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: PM2 PP4 PP3

• Not Met criteria codes: PM4 PM5 PVS1 BS3 BS1 BP3 BP4 PS3 PS1 BA1

Expert Panel

Familial Hypercholesterolemia VCEP

Criteria Specification Information

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