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]
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computed assertion could be determined for this classification!

Variant: NM_000527.5(LDLR):c.292G>T (p.Gly98Cys)

CA404075778

889190 (ClinVar)

Gene: LDLR
Condition: hypercholesterolemia, familial
Inheritance Mode: Semidominant inheritance
Link to MONDO
UUID: c7a6b16e-70ad-4257-b7c5-5f7d675507eb
Approved on: 2024-02-23
Published on: 2024-12-02

HGVS expressions

NM_000527.5:c.292G>T
NM_000527.5(LDLR):c.292G>T (p.Gly98Cys)
NC_000019.10:g.11102765G>T
CM000681.2:g.11102765G>T
NC_000019.9:g.11213441G>T
CM000681.1:g.11213441G>T
NC_000019.8:g.11074441G>T
NG_009060.1:g.18385G>T
ENST00000252444.10:c.550G>T
ENST00000559340.2:c.292G>T
ENST00000560467.2:c.292G>T
ENST00000558518.6:c.292G>T
ENST00000252444.9:c.546G>T
ENST00000455727.6:c.292G>T
ENST00000535915.5:c.190+2420G>T
ENST00000545707.5:c.292G>T
ENST00000557933.5:c.292G>T
ENST00000557958.1:n.378G>T
ENST00000558013.5:c.292G>T
ENST00000558518.5:c.292G>T
NM_000527.4:c.292G>T
NM_001195798.1:c.292G>T
NM_001195799.1:c.190+2420G>T
NM_001195800.1:c.292G>T
NM_001195803.1:c.292G>T
NM_001195798.2:c.292G>T
NM_001195799.2:c.190+2420G>T
NM_001195800.2:c.292G>T
NM_001195803.2:c.292G>T
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Uncertain Significance

Met criteria codes 1
PM2
Not Met criteria codes 24
PVS1 BA1 PM6 PM4 PM3 PM5 BS3 BS4 BS1 BS2 BP7 BP5 BP3 BP2 BP4 BP1 PS3 PS2 PS4 PS1 PP4 PP1 PP3 PP2

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

PDF
Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Familial Hypercholesterolemia VCEP
The NM_000527.5(LDLR):c.292G>T (p.Gly98Cys) variant is classified as Uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying ACMG/AMP evidence code PM2 as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (specification version 1.2) on 23 February 2024. The supporting evidence is as follows: PM2: This variant is absent from gnomAD (gnomAD v2.1.1).
Met criteria codes
PM2
This variant is absent from gnomAD (gnomAD v2.1.1).
Not Met criteria codes
PVS1
Missense variant; not applicable
BA1
This variant is absent from gnomAD (gnomAD v2.1.1).
PM6
No de novo occurrence
PM4
Not applicable
PM3
Not identified in index cases with more than 1 variant
PM5
3 other missense variants in the same codon: NM_000527.5(LDLR):c.292G>A (p.Gly98Ser) (ClinVar ID 251118): - Conflicting classifications of pathogenicity by these guidelines NM_000527.5(LDLR):c.292G>C (p.Gly98Arg) (ClinVar ID 251119) - Conflicting classifications of pathogenicity by these guidelines NM_000527.5(LDLR):c.293G>C (p.Gly98Ala) (ClinVar ID 920443) - Uncertain significance by these guidelines There are no variants in the same codon classified as Pathogenic by these guidelines
BS3
No published functional studies
BS4
No lack of segregation identified
BS1
This variant is absent from gnomAD (gnomAD v2.1.1).
BS2
Not identified in normolipidemic individuals
BP7
Not applicable
BP5
Not applicable
BP3
Not applicable
BP2
Not identified in index cases with more than 1 variant
BP4
REVEL = 0.692. It is not below 0.5
BP1
Not applicable
PS3
No published functional studies
PS2
No de novo occurrence
PS4
Not identified in FH index cases
PS1
3 other missense variants in the same codon: NM_000527.5(LDLR):c.292G>A (p.Gly98Ser) (ClinVar ID 251118): - Conflicting classifications of pathogenicity by these guidelines NM_000527.5(LDLR):c.292G>C (p.Gly98Arg) (ClinVar ID 251119) - Conflicting classifications of pathogenicity by these guidelines NM_000527.5(LDLR):c.293G>C (p.Gly98Ala) (ClinVar ID 920443) - Uncertain significance by these guidelines There are no variants in the same codon classified as Pathogenic by these guidelines
PP4
Not identified in FH index cases
PP1
Cosegregation not identified
PP3
REVEL = 0.692. It is not above 0.75, splicing evaluation needed. Functional data on splicing not available. A) Variant not on limits. B) Variant does not create a GT C) There is no GT nearby Variant is not predicted to alter splicing.
PP2
Not applicable
Curation History
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