Evidence Repository - Clinical Genome Resources

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Variant: NM_000527.5(LDLR):c.797A>T (p.Asp266Val)

CA10585137

251458 (ClinVar)

Gene: LDLR

Condition: hypercholesterolemia, familial

Inheritance Mode: Semidominant inheritance

Link to MONDO

UUID: 1170e266-2790-4fd8-9f99-c5add945f0d0

Approved on: 2021-11-14

Published on: 2022-06-30

HGVS expressions

NM_000527.5:c.797A>T

NM_000527.5(LDLR):c.797A>T (p.Asp266Val)

NC_000019.10:g.11106667A>T

CM000681.2:g.11106667A>T

NC_000019.9:g.11217343A>T

CM000681.1:g.11217343A>T

NC_000019.8:g.11078343A>T

NG_009060.1:g.22287A>T

ENST00000558518.6:c.797A>T

ENST00000252444.9:n.1051A>T

ENST00000455727.6:c.314-725A>T

ENST00000535915.5:c.674A>T

ENST00000545707.5:c.416A>T

ENST00000557933.5:c.797A>T

ENST00000558013.5:c.797A>T

ENST00000558518.5:c.797A>T

ENST00000558528.1:n.312A>T

ENST00000560467.1:n.397A>T

NM_000527.4:c.797A>T

NM_001195798.1:c.797A>T

NM_001195799.1:c.674A>T

NM_001195800.1:c.314-725A>T

NM_001195803.1:c.416A>T

NM_001195798.2:c.797A>T

NM_001195799.2:c.674A>T

NM_001195800.2:c.314-725A>T

NM_001195803.2:c.416A>T

Likely Pathogenic

PM5_Strong PP3 PM2

PVS1 BA1 BP3 BP2 BP4 BP1 BP7 BP5 BS2 BS4 BS3 BS1 PP4 PP1 PP2 PM4 PM3 PM1 PM6 PS2 PS4 PS3 PS1

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.797A>T (p.Asp266Val) variant is classified as Likely pathogenic for Familial Hypercholesterolemia by applying evidence codes PM5_Strong, PM2, and PP3 as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (https://doi.org/10.1101/2021.03.17.21252755). PM5_Strong - 4 other missense variants in the same codon: - NM_000527.5(LDLR): c.796G>T (p.Asp266Asn) (ClinVar ID 226334) - Pathogenic by these guidelines, - NM_000527.5(LDLR): c.797A>G (p.Asp266Gly) (ClinVar ID 251458) – Likely pathogenic by these guidelines, - NM_000527.5(LDLR): c.796A>T (p.Asp266Tyr) (ClinVar ID 251456) – Pathogenic by these guidelines, - NM_000527.5(LDLR): c.798T>A (p.Asp266Glu) - (ClinVar ID 161287) - Pathogenic by these guidelines. There are 3 variants in the same codon classified as Pathogenic by these guidelines; PM2 - This variant is absent from gnomAD (gnomAD v2.1.1); PP3 - REVEL = 0.97;

PM5_Strong

4 other missense variants in the same codon: - NM_000527.5(LDLR): c.796G>T (p.Asp266Asn) (ClinVar ID 226334) - Pathogenic by these guidelines, - NM_000527.5(LDLR): c.797A>G (p.Asp266Gly) (ClinVar ID 251458) – Likely pathogenic by these guidelines, - NM_000527.5(LDLR): c.796A>T (p.Asp266Tyr) (ClinVar ID 251456) – Pathogenic by these guidelines, - NM_000527.5(LDLR): c.798T>A (p.Asp266Glu) - (ClinVar ID 161287) - Pathogenic by these guidelines. There are 3 variants in the same codon classified as Pathogenic by these guidelines;

PP3

REVEL = 0.97

PM2

This variant is absent from gnomAD (gnomAD v2.1.1)

PVS1