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Variant: NM_000527.5(LDLR):c.169G>A (p.Asp57Asn)

CA10584771

251040 (ClinVar)

Gene: LDLR
Condition: hypercholesterolemia, familial
Inheritance Mode: Semidominant inheritance
UUID: 7db92565-5287-495d-97ef-45a26dd534ac

HGVS expressions

NM_000527.5:c.169G>A
NM_000527.5(LDLR):c.169G>A (p.Asp57Asn)
NC_000019.10:g.11100324G>A
CM000681.2:g.11100324G>A
NC_000019.9:g.11211000G>A
CM000681.1:g.11211000G>A
NC_000019.8:g.11072000G>A
NG_009060.1:g.15944G>A
ENST00000558518.6:c.169G>A
ENST00000252444.9:n.423G>A
ENST00000455727.6:c.169G>A
ENST00000535915.5:c.169G>A
ENST00000545707.5:c.169G>A
ENST00000557933.5:c.169G>A
ENST00000557958.1:n.255G>A
ENST00000558013.5:c.169G>A
ENST00000558518.5:c.169G>A
ENST00000560502.5:n.255G>A
NM_000527.4:c.169G>A
NM_001195798.1:c.169G>A
NM_001195799.1:c.169G>A
NM_001195800.1:c.169G>A
NM_001195803.1:c.169G>A
NM_001195798.2:c.169G>A
NM_001195799.2:c.169G>A
NM_001195800.2:c.169G>A
NM_001195803.2:c.169G>A

Uncertain Significance

Met criteria codes 3
PM2 PP4 PP3
Not Met criteria codes 10
PM4 PM5 PVS1 BS3 BS1 BP3 BP4 PS3 PS1 BA1

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.169G>A (p.Asp57Asn) variant is classified as Uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying evidence codes PM2, PP3, and PP4 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= 0.791. It is above 0.75, so PP3 is met. PP4: Variant meets PM2 and is identified in 1 case fulfilling WHO criteria published in PMID: 20145306 (Chmara et al., 2010). So PP4 is met.
Met criteria codes
PM2
This variant is absent from gnomAD (gnomAD v2.1.1.). So PM2 is met.
PP4
Variant meets PM2 and is identified in 1 case fulfilling WHO criteria published in PMID: 20145306 (Chmara et al., 2010). So PP4 is met.
PP3
REVEL= 0.791. It is above 0.75, so PP3 is met.
Not Met criteria codes
PM4
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.170A>G (p.Asp57Gly) (ClinVar ID 1380181) Uncertain significance by these guidelines -NM_000527.5(LDLR):c.170A>C (p.Asp57Ala) (ClinVar ID 523722) Uncertain significance by these guidelines
PVS1
Not a null variant
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.).
BP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP4
REVEL= 0.791. It is above 0.5
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.).
Approved on: 2022-08-29
Published on: 2022-12-23
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