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]

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Variant: NM_000527.5(LDLR):c.2113G>C (p.Ala705Pro)

CA023637

36459 (ClinVar)

Gene: LDLR

Condition: hypercholesterolemia, familial

Inheritance Mode: Semidominant inheritance

Link to MONDO

UUID: cc00e79a-6117-45c6-a00e-c5726b9419c4

HGVS expressions

NM_000527.5:c.2113G>C

NM_000527.5(LDLR):c.2113G>C (p.Ala705Pro)

NC_000019.10:g.11120495G>C

CM000681.2:g.11120495G>C

NC_000019.9:g.11231171G>C

CM000681.1:g.11231171G>C

NC_000019.8:g.11092171G>C

NG_009060.1:g.36115G>C

ENST00000558518.6:c.2113G>C

ENST00000252444.9:n.2367G>C

ENST00000455727.6:c.1609G>C

ENST00000535915.5:c.1990G>C

ENST00000545707.5:c.1606+262G>C

ENST00000557933.5:c.2113G>C

ENST00000558013.5:c.2113G>C

ENST00000558518.5:c.2113G>C

NM_000527.4:c.2113G>C

NM_001195798.1:c.2113G>C

NM_001195799.1:c.1990G>C

NM_001195800.1:c.1609G>C

NM_001195803.1:c.1606+262G>C

NM_001195798.2:c.2113G>C

NM_001195799.2:c.1990G>C

NM_001195800.2:c.1609G>C

NM_001195803.2:c.1606+262G>C

Uncertain Significance

PP3 PP4 PM2

PS3 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.2113G>C (p.Ala705Pro) variant is classified as Uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying evidence codes (PM2, PP4, 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 Met: PopMAX MAF = 0.00001 in European (Non-Finnish) population in gnomAD (gnomAD v2.1.1). PP4 Met: This variant meets PM2 and is identified in 1 index case who met clinical criteria for FH after alternative causes for high cholesterol were excluded (Department of Vascular Medicine, Academic Medical Center at the University of Amsterdam, Amsterdam, The Netherlands, PMID 11810272). PP3 Met: REVEL score = 0.78, which is above the threshold of 0.75. PS3 not met: There is no functional experiment reported for this variant. PM5 not met: There is one other variant in the same codon: LDLR: NM_000527:c.2113G>T (p.Ala705Ser) is classified as Uncertain significance - insufficient evidence by these guidelines. Therefore PM5 is not met.

PP3

REVEL score = 0.78, which is above the threshold of 0.75.

PP4

This variant meets PM2 and is identified in 1 index case who met clinical criteria for FH after alternative causes for high cholesterol were excluded (Department of Vascular Medicine, Academic Medical Center at the University of Amsterdam, Amsterdam, The Netherlands, PMID 11810272).

PM2

PopMAX MAF = 0.00001 in European (Non-Finnish) population in gnomAD (gnomAD v2.1.1).

PS3

There is no functional experiment reported for this variant.

PM5

There is one other variant in the same codon: LDLR: NM_000527:c.2113G>T (p.Ala705Ser) is classified as Uncertain significance - insufficient evidence by these guidelines. Therefore PM5 is not met.

Approved on: 2022-02-11

Published on: 2022-04-25

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