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

CA305287212

430740 (ClinVar)

Gene: N/A

Condition: hypercholesterolemia, familial

Inheritance Mode: Semidominant inheritance

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

• Met criteria codes: PM2

• Not Met criteria codes: BS4 BS3 BS1 BS2 BP7 BP2 BP4 BA1 PM6 PVS1 PM1 PM3 PM5 PM4 PS2 PS1 PS4 PS3 PP1 PP3 PP4

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

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.

Met criteria codes

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

Not Met criteria codes

• 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.
• BS2: No control individuals tested, so BS2 is Not Met.
• BP7: Variant is not synonymous, so BP7 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
• BA1: This variant is absent from gnomAD (gnomAD v2.1.1), so BA1 is not met.
• PM6: de novo occurrence data not reported, so PM6 is Not Met.
• PVS1: Variant is on 5'UTR, so PVS1 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.
• 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.
• 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.