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_000527.4(LDLR):c.2389+8C>T

CA040318

413774 (ClinVar)

Gene: LDLR

Condition: hypercholesterolemia, familial

Inheritance Mode: Semidominant inheritance

Link to MONDO

UUID: 2cfe8966-fc81-480a-a6f6-acad940dfe1d

HGVS expressions

NM_000527.4:c.2389+8C>T

NM_000527.4(LDLR):c.2389+8C>T

ENST00000558518.6:c.2389+8C>T

ENST00000252444.9:n.2643+8C>T

ENST00000455727.6:c.1885+8C>T

ENST00000535915.5:c.2266+8C>T

ENST00000545707.5:c.1855+8C>T

ENST00000557933.5:c.2389+8C>T

ENST00000558013.5:c.2389+8C>T

ENST00000558518.5:c.2389+8C>T

ENST00000560628.1:n.108+439C>T

NM_001195798.1:c.2389+8C>T

NM_001195799.1:c.2266+8C>T

NM_001195800.1:c.1885+8C>T

NM_001195803.1:c.1855+8C>T

NM_000527.5:c.2389+8C>T

NM_001195798.2:c.2389+8C>T

NM_001195799.2:c.2266+8C>T

NM_001195800.2:c.1885+8C>T

NM_001195803.2:c.1855+8C>T

NC_000019.10:g.11128093C>T

CM000681.2:g.11128093C>T

NC_000019.9:g.11238769C>T

CM000681.1:g.11238769C>T

NC_000019.8:g.11099769C>T

NG_009060.1:g.43713C>T

Uncertain Significance

BP4

PS2 PS4 PS3 PS1 PVS1 PP4 PP1 PP3 PP2 BA1 PM6 PM2 BS4 BS3 BS1 PM3 PM1 PM4 PM5 BS2 BP5 BP7 BP2 BP3 BP1

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_000527.4(LDLR):c.2389+8C>T variant is classified as variant of Uncertain significance for Familial Hypercholesterolemia by evaluating evidence codes (BP4) as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (https://doi.org/10.1101/2021.03.17.21252755). The supporting evidence is as follows: BP4 - no REVEL, splicing evaluation required. No functional assay on splicing. not on splicing limits, so BP4 is met.

BP4

no REVEL, splicing evaluation required. No functional assay on splicing. not on splicing limits, so BP4 is met

PS2

No de novo data available

PS4

PM2 caveat not met

PS3

No functional data available

PS1

NA; intronic

PVS1

NA; intronic, outside canonical splice sites

PP4

PM2 caveat not met

PP1

No segregation data available

PP3

no REVEL, splicing evaluation required. No functional assay on splicing. not on splicing limits

PP2

BA1

FAF = 0.001595 (0.16%) in East Asian exomes (gnomAD v2.1.1)

PM6

No de novo data available

PM2

PopMax MAF = 0.002506 (0.2506%) in East Asian exomes (gnomAD v2.1.1)

BS4

No segregation data available

BS3

No functional data available

BS1

FAF = 0.001595 (0.16%) in East Asian exomes (gnomAD v2.1.1)

PM3

PM2 caveat not met

PM1

NA; intronic

PM4

NA; intronic

PM5

NA; intronic

BS2

Not observed in data available

BP5

BP7

NA; intronic

BP2

Not observed in data available

BP3

BP1

Approved on: 2021-06-23

Published on: 2021-06-24

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