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.-286C>G

CA305287212

430740 (ClinVar)

Gene: N/A

Condition: hypercholesterolemia, familial

Inheritance Mode: Semidominant inheritance

Link to MONDO

UUID: 4731697f-56c4-4a30-9223-437e5bbf0068

Approved on: 2023-04-29

Published on: 2023-04-29

HGVS expressions

NM_000527.4(LDLR):c.-286C>G

NC_000019.10:g.11089263C>G

CM000681.2:g.11089263C>G

NC_000019.9:g.11199939C>G

CM000681.1:g.11199939C>G

NC_000019.8:g.11060939C>G

NG_009060.1:g.4883C>G

NR_163945.1:n.397G>C

Uncertain Significance

PM2

BA1 BS2 BS4 BS3 BS1 BP2 BP4 BP7 PS2 PS1 PS4 PS3 PVS1 PP1 PP3 PP4 PM1 PM3 PM5 PM4 PM6

Evidence Links 0

Expert Panel

Familial Hypercholesterolemia VCEP

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 NC_000019.10:g.11089263C>G variant is classified as Uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying evidence codes (PM2) 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 - This variant is absent from gnomAD (gnomAD v2.1.1), so PM2 is Met.

PM2

This variant is absent from gnomAD (gnomAD v2.1.1), so PM2 is Met.

BA1

This variant is absent from gnomAD (gnomAD v2.1.1), so BA1 is not met.

BS2

No control individuals tested, so BS2 is Not Met.

BS4

Lack of segregation data not reported, so BS4 is Not Met.

BS3

There are no functional studies reported for this variant, so BS3 is not met.

BS1

This variant is absent from gnomAD (gnomAD v2.1.1), so BS1 is not met.

BP2

Not observed in trans with other LP/P variants, so BP2 is Not Met.

BP4

Variant is on 5'UTR, so BP3 is is not applicable

BP7

Variant is not synonymous, so BP7 is Not Met.

PS2

de novo occurrence data not reported, so PS2 is Not Met.

PS1

Variant is in a non-coding region, so PS1 is Not Met.

PS4

Variant meets PM2, but data reported does not meet any validated criteria, so PS4 is Not Met.

PS3

There are no functional studies reported for this variant, so PS3 is not met.

PVS1

Variant is on 5'UTR, so PVS1 is Not Met.

PP1

Segregation data not reported, so PP1 is Not Met.

PP3

Variant is on 5'UTR, so PP3 is is not applicable.

PP4

Variant meets PM2, but data reported does not meet any validated criteria, so PP4 is Not Met.

PM1

Variant meets PM2 but is not located in exon 4 or alters a cysteine residues, so PM1 is Not Met.

PM3

Not observed in trans with other LP/P variants, so PM3 is Not Met.

PM5

Variant is in a non-coding region, so PM5 is Not Met.

PM4

Variant meets PM2 but is on 5'UTR, so PM4 is Not Met.

PM6

de novo occurrence data not reported, so PM6 is Not Met.

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