The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

  • See Evidence submitted by expert panel for details.

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

CA023637

36459 (ClinVar)

Gene: LDLR
Condition: hypercholesterolemia, familial
Inheritance Mode: Semidominant inheritance
UUID: cc00e79a-6117-45c6-a00e-c5726b9419c4
Approved on: 2022-02-11
Published on: 2022-04-25

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
More

Uncertain Significance

Met criteria codes 3
PM2 PP3 PP4
Not Met criteria codes 2
PM5 PS3

Evidence Links 0

Expert Panel

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.
Met criteria codes
PM2
PopMAX MAF = 0.00001 in European (Non-Finnish) population in gnomAD (gnomAD v2.1.1).
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).
Not Met criteria codes
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.
PS3
There is no functional experiment reported for this variant.
Curation History
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.
¤ Powered by BCM's Genboree.