Evidence Repository - Clinical Genome Resources

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

Link to SEPIO compliant JSON-LD document

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

CA023645

36460 (ClinVar)

Gene: LDLR

Condition: hypercholesterolemia, familial

Inheritance Mode: Semidominant inheritance

Link to MONDO

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

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

BA1 BS3_Supporting

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

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.

BA1

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

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.

PM3

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

PM1

Intronic variant. Not applicable.

PM4

Intronic variant. Not applicable.

PM5

Intronic variant. 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%.

PVS1

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

BS2

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

BS4

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.

BP5

Not applicable.

BP7

Intronic variant. Not applicable.

BP2

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

BP3

Not applicable.

BP4

Functional data available. Not applicable.

BP1

Not applicable.

PS2

No de novo cases were identified.

PS4

PM2 is not met. Not applicable.

PS3

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

PS1

Intronic variant. Not applicable.

PP4

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.

PP3

Functional data available. Not applicable.

PP2

Not applicable.

Approved on: 2021-06-18

Published on: 2021-06-24

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