NM_000527.5(LDLR):c.1987+10G>T AND Hypercholesterolemia, familial, 1

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Mar 24, 2025
Review status:: 3 stars out of maximum of 4 stars
reviewed by expert panel

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000238481.2

Allele description [Variation Report for NM_000527.5(LDLR):c.1987+10G>T]

NM_000527.5(LDLR):c.1987+10G>T

Gene:

LDLR:low density lipoprotein receptor [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

19p13.2

Genomic location:

Preferred name:

NM_000527.5(LDLR):c.1987+10G>T

HGVS:

NC_000019.10:g.11120243G>T
NG_009060.1:g.35863G>T
NM_000527.5:c.1987+10G>TMANE SELECT
NM_001195798.2:c.1987+10G>T
NM_001195799.2:c.1864+10G>T
NM_001195800.2:c.1483+10G>T
NM_001195803.2:c.1606+10G>T
LRG_274t1:c.1987+10G>T
LRG_274:g.35863G>T
NC_000019.9:g.11230919G>T
NM_000527.4:c.1987+10G>T
c.1987+10G>T

Links:

LDLR-LOVD, British Heart Foundation: LDLR_000269; dbSNP: rs375846192

Molecular consequence:

NM_000527.5:c.1987+10G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001195798.2:c.1987+10G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001195799.2:c.1864+10G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001195800.2:c.1483+10G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001195803.2:c.1606+10G>T - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:: Hypercholesterolemia, familial, 1
Synonyms:: LDL RECEPTOR DISORDER; Hyperlipoproteinemia Type IIa; HYPER-LOW-DENSITY-LIPOPROTEINEMIA; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0007750; MedGen: C0745103; Orphanet: 391665; OMIM: 143890

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000295795	LDLR-LOVD, British Heart Foundation	criteria provided, single submitter (ACGS Guidelines, 2013)	Likely benign (Mar 25, 2016)	germline	research	Citation Link,
SCV007432528	ClinGen Familial Hypercholesterolemia Variant Curation Expert Panel	reviewed by expert panel (ClinGen FH ACMG Specifications v1-2)	Uncertain Significance (Mar 24, 2025)	germline	curation	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000295795

LDLR-LOVD, British Heart Foundation

criteria provided, single submitter

(ACGS Guidelines, 2013)

Likely benign
(Mar 25, 2016)

germline

research

Citation Link,

SCV007432528

ClinGen Familial Hypercholesterolemia Variant Curation Expert Panel

reviewed by expert panel

(ClinGen FH ACMG Specifications v1-2)

Uncertain Significance
(Mar 24, 2025)

germline

curation

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	curation
not provided	germline	yes	1	not provided	not provided	1	not provided	research

Details of each submission

From LDLR-LOVD, British Heart Foundation, SCV000295795.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	research	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	1	not provided	not provided		1	not provided	not provided	not provided

From ClinGen Familial Hypercholesterolemia Variant Curation Expert Panel, SCV007432528.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	not provided

Description

The NM_000527.5(LDLR):c.1987+10G>T variant is classified as Uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying ACMG/AMP evidence codes PM2, PP4, PS4_Supporting and BP4 as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (specification version 1.2) on 24 March 2025. The supporting evidence is as follows: PM2: PopMax MAF = 0.00008220 (0.00822%) in Non-Finnish European (gnomAD v4.1.0). PS4_Supporting, PP4: Variant meets PM2 and is identified in 2 unrelated cases who fulfill Simon Broome criteria for possible FH from Centre de Génétique Moléculaire et Chromosomique, Unité de génétique de l'Obésité et des Dyslipidémies, APHP.Sorbonne Université, Hôpital de la Pitié-Salpêtrière, France. BP4: No REVEL, splicing evaluation required. SpliceAI: acceptor loss = 0.01, donor loss = 0.04. Variant is not predicted to alter splicing.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Apr 12, 2026

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