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.1061-8T>C

CA023412

36451 (ClinVar)

Gene: LDLR

Condition: hypercholesterolemia, familial

Inheritance Mode: Semidominant inheritance

Link to MONDO

UUID: ae8305b5-add5-4562-92bb-5b2df2ce6396

HGVS expressions

NM_000527.5:c.1061-8T>C

NM_000527.5(LDLR):c.1061-8T>C

NC_000019.10:g.11111506T>C

CM000681.2:g.11111506T>C

NC_000019.9:g.11222182T>C

CM000681.1:g.11222182T>C

NC_000019.8:g.11083182T>C

NG_009060.1:g.27126T>C

ENST00000558518.6:c.1061-8T>C

ENST00000252444.9:n.1315-8T>C

ENST00000455727.6:c.557-8T>C

ENST00000535915.5:c.938-8T>C

ENST00000545707.5:c.680-8T>C

ENST00000557933.5:c.1061-8T>C

ENST00000558013.5:c.1061-8T>C

ENST00000558518.5:c.1061-8T>C

ENST00000560173.1:n.60-8T>C

ENST00000560467.1:n.541-8T>C

NM_000527.4:c.1061-8T>C

NM_001195798.1:c.1061-8T>C

NM_001195799.1:c.938-8T>C

NM_001195800.1:c.557-8T>C

NM_001195803.1:c.680-8T>C

NM_001195798.2:c.1061-8T>C

NM_001195799.2:c.938-8T>C

NM_001195800.2:c.557-8T>C

NM_001195803.2:c.680-8T>C

Benign

BA1 BS3_Supporting

BP2

Evidence Links 0

Expert Panel

Familial Hypercholesterolemia VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Familial Hypercholesterolemia VCEP

The NM_000527.5 (LDLR):c.1061-8T>C 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/10.1016/j.gim.2021.09.012). The supporting evidence is as follows: BA1: PopMax FAF = 0.008564 in African/African American population in gnomAD (gnomAD v2.2.1). BS3_Supporting: Heterozygous patient cells were used for RNA assays (Level 3 experiment) shown normal LDLR transcripts reported from 2 research labs: Bourbon et al, Unidade de Investigacao Cardiovascular, Instituto Nacional de Saude Dr. Ricardo Jorge, Lisboa, Portugal, (PMID 19411563); Holla et al, Medical Genetics Laboratory, Department of Medical Genetics, Rikshospitalet University Hospital, Oslo, Norway, (PMID 19208450). Functional studies is consistent with no damaging effect.

BA1

PopMax FAF = 0.008564 in African/African American population in gnomAD (gnomAD v2.2.1).

BS3_Supporting

Heterozygous patient cells were used for RNA assays (Level 3 experiment) shown normal LDLR transcripts reported from 2 research labs: Bourbon et al, Unidade de Investigacao Cardiovascular, Instituto Nacional de Saude Dr. Ricardo Jorge, Lisboa, Portugal, (PMID 19411563); Holla et al, Medical Genetics Laboratory, Department of Medical Genetics, Rikshospitalet University Hospital, Oslo, Norway, (PMID 19208450). Functional studies is consistent with no damaging effect.

BP2

At least 2 index cases also carry LDLR:c.2177C>T,p.T726I, identified from 2 different labs. One case was confirmed that 2 variants are in trans (Cardiovascular Research Group,Instituto Nacional de Saude Doutor Ricardo Jorge); 1 case was identified with unknown phase of 2 variants (Robarts Research Institute). Variant LDLR:c.2177C>T,p.T726I is classified as Benign by these guidelines, therefore BP2 is not met.

Approved on: 2022-03-25

Published on: 2022-04-25

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.