chr1-21814785-G-T

Position:

• chr1-21814785-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001013693.3(LDLRAD2):​c.473G>T​(p.Arg158Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LDLRAD2 NM_001013693.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.12

Genes affected

LDLRAD2 (HGNC:32071): (low density lipoprotein receptor class A domain containing 2) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LDLRAD2	NM_001013693.3	c.473G>T	p.Arg158Leu	missense_variant	2/5	ENST00000344642.7	NP_001013715.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LDLRAD2	ENST00000344642.7	c.473G>T	p.Arg158Leu	missense_variant	2/5	2	NM_001013693.3	ENSP00000340988.2
LDLRAD2	ENST00000543870.1	c.473G>T	p.Arg158Leu	missense_variant	2/6	1		ENSP00000444097.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1327436 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 649572

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 14, 2024

The c.473G>T (p.R158L) alteration is located in exon 2 (coding exon 2) of the LDLRAD2 gene. This alteration results from a G to T substitution at nucleotide position 473, causing the arginine (R) at amino acid position 158 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.65
BayesDel_addAF	Uncertain	0.069	T
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T;T
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.85	.;T
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.69	D;D
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.4	M;M
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-2.9	D;D
REVEL	Benign	0.21
Sift	Benign	0.17	T;T
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.93	P;P
Vest4		0.64
MutPred		0.55		Loss of disorder (P = 0.0665);Loss of disorder (P = 0.0665);
MVP		0.58
MPC		1.0
ClinPred		0.99	D
GERP RS		4.7
Varity_R		0.28
gMVP		0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-22141278;