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.1765G>T (p.Asp589Tyr)

CA404089744

441222 (ClinVar)

Gene: LDLR
Condition: hypercholesterolemia, familial
Inheritance Mode: Semidominant inheritance
Link to MONDO
UUID: 1b4f0fbc-a84a-4f48-aa0f-7ba01610c065

HGVS expressions

NM_000527.5:c.1765G>T
NM_000527.5(LDLR):c.1765G>T (p.Asp589Tyr)
NC_000019.10:g.11116918G>T
CM000681.2:g.11116918G>T
NC_000019.9:g.11227594G>T
CM000681.1:g.11227594G>T
NC_000019.8:g.11088594G>T
NG_009060.1:g.32538G>T
ENST00000558518.6:c.1765G>T
ENST00000252444.9:n.2019G>T
ENST00000455727.6:c.1261G>T
ENST00000535915.5:c.1642G>T
ENST00000545707.5:c.1384G>T
ENST00000557933.5:c.1765G>T
ENST00000558013.5:c.1765G>T
ENST00000558518.5:c.1765G>T
ENST00000559340.1:n.426+706G>T
NM_000527.4:c.1765G>T
NM_001195798.1:c.1765G>T
NM_001195799.1:c.1642G>T
NM_001195800.1:c.1261G>T
NM_001195803.1:c.1384G>T
NM_001195798.2:c.1765G>T
NM_001195799.2:c.1642G>T
NM_001195800.2:c.1261G>T
NM_001195803.2:c.1384G>T

Uncertain Significance

Met criteria codes 2
PM2 BP4
Not Met criteria codes 3
PS4 PP3 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.1765G>T (p.Asp589Tyr) variant is classified as Uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying evidence codes PM2 and BP4 as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (https://doi.org/10.1016/j.gim.2021.09.012). PM2 - This variant is absent from gnomAD (gnomAD v2.1.1), so PM2 is met. BP4 - REVEL = 0.447. It is not above 0.75, splicing evaluation needed. Functional data on splicing not available. A) variant not on limits. B) does not create AG or GT Variant is not predicted to alter splicing
Met criteria codes
PM2
This variant is absent from gnomAD (gnomAD v2.1.1), so PM2 is met.
BP4
BP4: REVEL = 0.447. It is not above 0.75, splicing evaluation needed. Functional data on splicing not available. A) variant not on limits. B) does not create AG or GT Variant is not predicted to alter splicing
Not Met criteria codes
PS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Approved on: 2022-08-29
Published on: 2022-12-23
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