Evidence Repository - GenboreeKB

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_000527.5(LDLR):c.2140+5G>A

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA023645

36460 (ClinVar)

Gene: LDLR

Condition: hypercholesterolemia, familial

Inheritance Mode: Semidominant inheritance

Link to MONDO

UUID: 56e1a7d8-b14a-4759-be2e-3a9ea6668dec

Approved on: 2021-06-18

Published on: 2021-06-24

HGVS expressions

NM_000527.5:c.2140+5G>A

NM_000527.5(LDLR):c.2140+5G>A

NC_000019.10:g.11120527G>A

CM000681.2:g.11120527G>A

NC_000019.9:g.11231203G>A

CM000681.1:g.11231203G>A

NC_000019.8:g.11092203G>A

NG_009060.1:g.36147G>A

ENST00000558518.6:c.2140+5G>A

ENST00000252444.9:n.2394+5G>A

ENST00000455727.6:c.1636+5G>A

ENST00000535915.5:c.2017+5G>A

ENST00000545707.5:c.1606+294G>A

ENST00000557933.5:c.2140+5G>A

ENST00000558013.5:c.2140+5G>A

ENST00000558518.5:c.2140+5G>A

NM_000527.4:c.2140+5G>A

NM_001195798.1:c.2140+5G>A

NM_001195799.1:c.2017+5G>A

NM_001195800.1:c.1636+5G>A

NM_001195803.1:c.1606+294G>A

NM_001195798.2:c.2140+5G>A

NM_001195799.2:c.2017+5G>A

NM_001195800.2:c.1636+5G>A

NM_001195803.2:c.1606+294G>A

Benign

BS3_Supporting BA1

BS2 BS1 BS4 BP5 BP7 BP3 BP1 BP2 BP4 PS1 PS2 PS3 PS4 PP1 PP2 PP3 PP4 PM1 PM3 PM5 PM4 PVS1 PM6 PM2

Evidence Links 0

Expert Panel

Familial Hypercholesterolemia VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Familial Hypercholesterolemia VCEP

NM_000527.5(LDLR):c.2140+5G>A variant is classified as Benign for Familial Hypercholesterolemia by applying evidence codes (BA1, BS3_Supporting) as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (https://doi.org/10.1101/2021.03.17.21252755). The supporting evidence is as follows: BA1 - FAF = 0.01030 (1.030%) in European non-Finnish exomes (gnomAD v2.1.1). BS3_supporting - Level 3 assay: PMID:19208450 - study on patient's lymphocytes, Northern blot + real-time PCR + FACS used: normal mRNA processing + 108% low-density lipoprotein receptor activity. ---- functional study is consistent with no damaging effect.

BS3_Supporting

Level 3 assay: PMID:19208450 - study on patient's lymphocytes, Northern blot + real-time PCR + FACS used: normal mRNA processing + 108% low-density lipoprotein receptor activity. ---- functional study is consistent with no damaging effect.

BA1

FAF = 0.01030 (1.030%) in European non-Finnish exomes (gnomAD v2.1.1). FAF is above 0.5%

BS2

Most of labs do not track clinical data in this variant due to classifying as benign in the past.

BS1

BA1 is met. Not applicable.

BS4

Most of labs do not track clinical data in this variant due to classifying as benign in the past.

BP5

Not applicable.

BP7

Intronic variant. Not applicable.

BP3

Not applicable.

BP1

Not applicable.

BP2

Most of labs do not track clinical data in this variant due to classifying as benign in the past.

BP4

Functional data available. Not applicable.

PS1

Intronic variant. Not applicable.

PS2

No de novo cases were identified.

PS3

No well established in vitro or in vivo functional studies supportive of a damaging effect on the gene or gene product.

PS4

PM2 is not met. Not applicable.

PP1

Most of labs do not track clinical data in this variant due to classifying as benign in the past.

PP2

Not applicable.

PP3

Functional data available. Not applicable.

PP4

PM2 is not met. Not applicable.

PM1

Intronic variant. Not applicable.

PM3

Most of labs do not track clinical data in this variant due to classifying as benign in the past.

PM5

Intronic variant. Not applicable.

PM4

Intronic variant. Not applicable.

PVS1

Intronic variant outside the canonical +/- 1 or 2 splice sites. Not applicable.

PM6

No de novo cases were identified.

PM2

PopMax MAF = 0.03088 (3.1%) in Ashkenazi Jewish exomes (gnomAD v2.1.1). FAF is not below 0.02%.

Curation History

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