NM_001013693.3:c.7G>T

Variant names:

• chr1-21812458-G-T
• rs369934300
• NM_001013693.3:c.7G>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001013693.3(LDLRAD2):​c.7G>T​(p.Ala3Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A3P) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: LDLRAD2 NM_001013693.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.506

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.061222076).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LDLRAD2	NM_001013693.3	c.7G>T	p.Ala3Ser	missense_variant	Exon 1 of 5	ENST00000344642.7	NP_001013715.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LDLRAD2	ENST00000344642.7	c.7G>T	p.Ala3Ser	missense_variant	Exon 1 of 5	2	NM_001013693.3	ENSP00000340988.2
LDLRAD2	ENST00000543870.1	c.7G>T	p.Ala3Ser	missense_variant	Exon 1 of 6	1		ENSP00000444097.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Bravo AF: 0.0000189

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	6.7
DANN	Benign	0.97
DEOGEN2	Benign	0.012	T;T
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.26	.;T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.061	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.90	L;L
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	0.21	N;N
REVEL	Benign	0.034
Sift	Benign	0.58	T;T
Sift4G	Benign	0.077	T;T
Vest4		0.083
MVP		0.27
MPC		0.30
ClinPred		0.082	T
GERP RS		-5.0
Varity_R		0.036
gMVP		0.46

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

LitVar

Other links and lift over

dbSNP: rs369934300; hg19: chr1-22138951;