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

Variant: NM_000527.5(LDLR):c.1836C>T (p.Ala612=)

CA036837

224618 (ClinVar)

Gene: LDLR
Condition: hypercholesterolemia, familial
Inheritance Mode: Semidominant inheritance
Link to MONDO
UUID: 7ca66b0a-7663-40c0-9d87-1cd640a32c28
Approved on: 2023-04-28
Published on: 2023-05-01

HGVS expressions

NM_000527.5:c.1836C>T
NM_000527.5(LDLR):c.1836C>T (p.Ala612=)
NC_000019.10:g.11116989C>T
CM000681.2:g.11116989C>T
NC_000019.9:g.11227665C>T
CM000681.1:g.11227665C>T
NC_000019.8:g.11088665C>T
NG_009060.1:g.32609C>T
ENST00000558518.6:c.1836C>T
ENST00000252444.9:n.2090C>T
ENST00000455727.6:c.1332C>T
ENST00000535915.5:c.1713C>T
ENST00000545707.5:c.1455C>T
ENST00000557933.5:c.1836C>T
ENST00000558013.5:c.1836C>T
ENST00000558518.5:c.1836C>T
ENST00000559340.1:n.426+777C>T
NM_000527.4:c.1836C>T
NM_001195798.1:c.1836C>T
NM_001195799.1:c.1713C>T
NM_001195800.1:c.1332C>T
NM_001195803.1:c.1455C>T
NM_001195798.2:c.1836C>T
NM_001195799.2:c.1713C>T
NM_001195800.2:c.1332C>T
NM_001195803.2:c.1455C>T
More

Likely Benign

Met criteria codes 2
BP4 BP7
Not Met criteria codes 2
BA1 BS1

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen Familial Hypercholesterolemia Expert Panel Specifications to the ACMG/AMP Variant Classification Guidelines Version 1.2

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Familial Hypercholesterolemia VCEP
The NM_000527.5(LDLR):c.1836C>T (p.Ala612=) variant is classified as likely benign for Familial Hypercholesterolemia by applying evidence code BP4 and BP7 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: BP4 - No REVEL, splicing evaluation required. Functional data on splicing not available. - Variant is exonic and at least 50bp downstream from canonical acceptor site but it does not create GT. - There is a GT nearby. MES scores: variant cryptic = -16.82, wt cryptic = -12.61, canonical donor = 4.48. Ratio variant cryptic/wt cryptic: -16.82/-12.61 = 1.33 --- it is above 1.1 Ratio variant cryptic/canonical donor: -16.82/4.48 = -3.75 --- it is not above 0.9 Variant is not predicted to alter splicing. BP7 - Variant is synonymous and meets BP4.
Met criteria codes
BP4
No REVEL, splicing evaluation required. - Variant is exonic and at least 50bp downstream from canonical acceptor site but it does not create GT. - There is a GT nearby. MES scores: variant cryptic = -16.82, wt cryptic = -12.61, canonical donor = 4.48. Ratio variant cryptic/wt cryptic: -16.82/-12.61 = 1.33 --- it is above 1.1 Ratio variant cryptic/canonical donor: -16.82/4.48 = -3.75 --- it is not above 0.9 Variant is not predicted to alter splicing.
BP7
Variant is synonymous and meets BP4.
Not Met criteria codes
BA1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS1
PopMax FAF = 0.0002341 (0.03%) in European (non -Finnish) exomes (gnomAD v2.1.1). It is between (0.0002 and 0.002)
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.