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.2530G>A (p.Gly844Ser)

CA404099832

440701 (ClinVar)

Gene: LDLR

Condition: hypercholesterolemia, familial

Inheritance Mode: Semidominant inheritance

Link to MONDO

UUID: ec627d37-6749-4608-a64e-6591b92a0eef

HGVS expressions

NM_000527.5:c.2530G>A

NM_000527.5(LDLR):c.2530G>A (p.Gly844Ser)

NC_000019.10:g.11129653G>A

CM000681.2:g.11129653G>A

NC_000019.9:g.11240329G>A

CM000681.1:g.11240329G>A

NC_000019.8:g.11101329G>A

NG_009060.1:g.45273G>A

ENST00000558518.6:c.2530G>A

ENST00000252444.9:n.2784G>A

ENST00000455727.6:c.2026G>A

ENST00000535915.5:c.2407G>A

ENST00000545707.5:c.1996G>A

ENST00000557933.5:c.2592G>A

ENST00000558013.5:c.2530G>A

ENST00000558518.5:c.2530G>A

ENST00000560628.1:n.108+1999G>A

NM_000527.4:c.2530G>A

NM_001195798.1:c.2530G>A

NM_001195799.1:c.2407G>A

NM_001195800.1:c.2026G>A

NM_001195803.1:c.1996G>A

NM_001195798.2:c.2530G>A

NM_001195799.2:c.2407G>A

NM_001195800.2:c.2026G>A

NM_001195803.2:c.1996G>A

Uncertain Significance

PP3 PM2

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

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Familial Hypercholesterolemia VCEP

The NM_000527.5 (LDLR):c.2530G>A (p.Gly844Ser) variant is classified as Uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying evidence codes (PM2, PP3) as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (https://doi.org/10.1016/j.gim.2021.09.012). The supporting evidence is as follows: PM2: This variant is absent from gnomAD (gnomAD 2.1.1). PP3: REVEL = 0.875. PM5 not met: One other variant in the same codon: -NM_000527.5:c.2531G>A (Gly844Asp) is classified as Likely Pathogenic by these guidelines, therefore PM5 is not met.

PP3

REVEL = 0.875

PM2

This variant is absent from gnomAD (gnomAD 2.1.1).

Approved on: 2023-03-20

Published on: 2023-03-31

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.