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.2375T>C (p.Ile792Thr)

CA040016

252295 (ClinVar)

Gene: LDLR

Condition: hypercholesterolemia, familial

Inheritance Mode: Semidominant inheritance

Link to MONDO

UUID: 08edf0a6-3b51-4484-b172-bc1e18ae8e44

HGVS expressions

NM_000527.5:c.2375T>C

NM_000527.5(LDLR):c.2375T>C (p.Ile792Thr)

NC_000019.10:g.11128071T>C

CM000681.2:g.11128071T>C

NC_000019.9:g.11238747T>C

CM000681.1:g.11238747T>C

NC_000019.8:g.11099747T>C

NG_009060.1:g.43691T>C

ENST00000558518.6:c.2375T>C

ENST00000252444.9:n.2629T>C

ENST00000455727.6:c.1871T>C

ENST00000535915.5:c.2252T>C

ENST00000545707.5:c.1841T>C

ENST00000557933.5:c.2375T>C

ENST00000558013.5:c.2375T>C

ENST00000558518.5:c.2375T>C

ENST00000560628.1:n.108+417T>C

NM_000527.4:c.2375T>C

NM_001195798.1:c.2375T>C

NM_001195799.1:c.2252T>C

NM_001195800.1:c.1871T>C

NM_001195803.1:c.1841T>C

NM_001195798.2:c.2375T>C

NM_001195799.2:c.2252T>C

NM_001195800.2:c.1871T>C

NM_001195803.2:c.1841T>C

Uncertain Significance

PP3

PS3 PM2 PM5

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.2375T>C (p. Ile792Thr) variant is classified as Uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying evidence codes (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: PP3: REVEL = 0.773. PM2 not met: PopMax MAF = 0.00056 in Latino population in gnomAD (gnomAD version: 2.1.1). PP4, PS4 not applicable: Variant did not meet PM2. PS3 not met: Functional data is not available. PM5 not met: There is one other variant in the same codon: LDLR: NM_000527:c.2374A>T (p.Ile792Phe) is classified as Uncertain significance - insufficient evidence by these guidelines. Therefore PM5 is not met.

PP3

REVEL = 0.773.

PS3

Functional data is not available.

PM2

PopMax MAF = 0.00056 in Latino population in gnomAD (gnomAD version: 2.1.1).

PM5

There is one other variant in the same codon: LDLR: NM_000527:c.2374A>T (p.Ile792Phe) is classified as Uncertain significance - insufficient evidence by these guidelines. Therefore PM5 is not met.

Approved on: 2022-08-26

Published on: 2022-12-23

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