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]
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Variant: NM_000527.5(LDLR):c.170A>C (p.Asp57Ala)

CA404075004

523722 (ClinVar)

Gene: LDLR
Condition: hypercholesterolemia, familial
Inheritance Mode: Semidominant inheritance
Link to MONDO
UUID: cf402cf5-6041-4c9f-8b0b-38094f351c3f

HGVS expressions

NM_000527.5:c.170A>C
NM_000527.5(LDLR):c.170A>C (p.Asp57Ala)
NC_000019.10:g.11100325A>C
CM000681.2:g.11100325A>C
NC_000019.9:g.11211001A>C
CM000681.1:g.11211001A>C
NC_000019.8:g.11072001A>C
NG_009060.1:g.15945A>C
ENST00000558518.6:c.170A>C
ENST00000252444.9:n.424A>C
ENST00000455727.6:c.170A>C
ENST00000535915.5:c.170A>C
ENST00000545707.5:c.170A>C
ENST00000557933.5:c.170A>C
ENST00000557958.1:n.256A>C
ENST00000558013.5:c.170A>C
ENST00000558518.5:c.170A>C
ENST00000560502.5:n.256A>C
NM_000527.4:c.170A>C
NM_001195798.1:c.170A>C
NM_001195799.1:c.170A>C
NM_001195800.1:c.170A>C
NM_001195803.1:c.170A>C
NM_001195798.2:c.170A>C
NM_001195799.2:c.170A>C
NM_001195800.2:c.170A>C
NM_001195803.2:c.170A>C

Uncertain Significance

Met criteria codes 2
PP3 PM2
Not Met criteria codes 16
BS2 BS4 BS3 BS1 BP2 BP4 PS4 PS2 PS3 PS1 BA1 PP1 PP4 PM6 PM3 PM5

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
Familial Hypercholesterolemia VCEP
The NM_000527.5(LDLR):c.170A>C (p.Asp57Ala) variant is classified as Uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying evidence codes PM2 and PP3 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. PP3: REVEL= 0.959. It is above 0.75, so PP3 is met.
Met criteria codes
PP3
PP3: REVEL= 0.959. It is above 0.75, so PP3 is met.
PM2
This variant is absent from gnomAD (gnomAD v2.1.1.). So PM2 is met.
Not Met criteria codes
BS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS1
This variant is absent from gnomAD (gnomAD v2.1.1.).
BP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP4
PP3: REVEL= 0.959. It is above 0.5
PS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BA1
This variant is absent from gnomAD (gnomAD v2.1.1.).
PP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM6
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM5
Two other missense variants in the same codon: - NM_000527.5(LDLR):c.169G>A (p.Asp57Asn) (ClinVar ID 251040) Uncertain significance by these guidelines - NM_000527.5(LDLR):c.170A>G (p.Asp57Gly) (ClinVar ID 1380181) Uncertain significance by these guidelines
Approved on: 2022-08-29
Published on: 2022-12-23
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