NM_001013693.3:c.446G>C

Variant names:

• chr1-21814758-G-C
• rs751993242
• NM_001013693.3:c.446G>C

Variant summary

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

The NM_001013693.3(LDLRAD2):​c.446G>C​(p.Arg149Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000737 in 1,356,422 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R149L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: LDLRAD2 NM_001013693.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.39

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 rank	MANE	Protein	UniProt
LDLRAD2	NM_001013693.3	c.446G>C	p.Arg149Pro	missense_variant	Exon 2 of 5	ENST00000344642.7	NP_001013715.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LDLRAD2	ENST00000344642.7	c.446G>C	p.Arg149Pro	missense_variant	Exon 2 of 5	2	NM_001013693.3	ENSP00000340988.2
LDLRAD2	ENST00000543870.1	c.446G>C	p.Arg149Pro	missense_variant	Exon 2 of 6	1		ENSP00000444097.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.37e-7 AC: 1 AN: 1356422 Hom.: 0 Cov.: 35 AF XY: 0.00000150 AC XY: 1 AN XY: 667182

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: 0.0000137

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.90
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.11
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.26	T;T
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.85	.;T
M_CAP	Benign	0.048	D
MetaRNN	Uncertain	0.70	D;D
MetaSVM	Benign	-0.51	T
MutationAssessor	Uncertain	2.4	M;M
PrimateAI	Uncertain	0.65	T
PROVEAN	Pathogenic	-4.6	D;D
REVEL	Uncertain	0.34
Sift	Uncertain	0.019	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;D
Vest4		0.52
MutPred		0.43		Loss of MoRF binding (P = 0.0181);Loss of MoRF binding (P = 0.0181);
MVP		0.67
MPC		1.3
ClinPred		0.98	D
GERP RS		5.1
Varity_R		0.82
gMVP		0.87

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: rs751993242; hg19: chr1-22141251;