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]

Variant: NM_000527.5(LDLR):c.2089G>A (p.Ala697Thr)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA038513

440678 (ClinVar)

Gene: LDLR

Condition: hypercholesterolemia, familial

Inheritance Mode: Semidominant inheritance

Link to MONDO

UUID: 894c9756-9a96-49a6-be08-dfa969d92d1a

Approved on: 2024-10-28

Published on: 2025-01-19

HGVS expressions

NM_000527.5:c.2089G>A

NM_000527.5(LDLR):c.2089G>A (p.Ala697Thr)

NC_000019.10:g.11120471G>A

CM000681.2:g.11120471G>A

NC_000019.9:g.11231147G>A

CM000681.1:g.11231147G>A

NC_000019.8:g.11092147G>A

NG_009060.1:g.36091G>A

ENST00000252444.10:c.2347G>A

ENST00000559340.2:c.*158G>A

ENST00000560467.2:c.1969G>A

ENST00000558518.6:c.2089G>A

ENST00000252444.9:c.2343G>A

ENST00000455727.6:c.1585G>A

ENST00000535915.5:c.1966G>A

ENST00000545707.5:c.1606+238G>A

ENST00000557933.5:c.2089G>A

ENST00000558013.5:c.2089G>A

ENST00000558518.5:c.2089G>A

NM_000527.4:c.2089G>A

NM_001195798.1:c.2089G>A

NM_001195799.1:c.1966G>A

NM_001195800.1:c.1585G>A

NM_001195803.1:c.1606+238G>A

NM_001195798.2:c.2089G>A

NM_001195799.2:c.1966G>A

NM_001195800.2:c.1585G>A

NM_001195803.2:c.1606+238G>A

Uncertain Significance

PP3 PM2

PS3 PS4 PP4 PM5

Evidence Links 0

Expert Panel

Familial Hypercholesterolemia VCEP

Criteria Specification Information

Criteria Specification: ClinGen Familial Hypercholesterolemia Expert Panel Specifications to the ACMG/AMP Variant Classification Guidelines Version 1.2

PDF

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Familial Hypercholesterolemia VCEP

The NM_000527.5 (LDLR):c.2089G>A (p.Ala697Thr) variant is classified as Uncertain significance – insufficient evidence for Familial Hypercholesterolemia by applying ACMG/AMP evidence codes PM2 and PP3 as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (specification version 1.2) on 28 October 2024. The supporting evidence is as follows: PM2: PopMax MAF=0.00002196 in South Asian exomes (gnomAD v4.1.0). PP3: REVEL=0.815.

PP3

REVEL=0.815, which is above the impact threshold.

PM2

PopMaxMAF=0.00002196 in South Asian exomes (gnomAD v4.1.0).

PS3

Functional data is not available.

PS4

Clinical data is not available.

PP4

Clinical data is not available.

PM5

One other variant in the same codon: NM_000527.5 (LDLR):c. 2089G>C (p.Ala697Pro)(ClinVarID 252213) is classified as VUS by these guidelines. Therefore, PM5 is not met.

Curation History

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.