14-93939153-C-G

Variant names:

• chr14-93939153-C-G
• rs540542265
• NM_001202429.2:c.1572G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001202429.2(ASB2):​c.1572G>C​(p.Arg524Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000014 in 1,426,240 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ASB2 NM_001202429.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.968

Genes affected

ASB2 (HGNC:16012): (ankyrin repeat and SOCS box containing 2) This gene encodes a member of the ankyrin repeat and SOCS box-containing (ASB) protein family. These proteins play a role in protein degradation by coupling suppressor of cytokine signalling (SOCS) proteins with the elongin BC complex. The encoded protein is a subunit of a multimeric E3 ubiquitin ligase complex that mediates the degradation of actin-binding proteins. This gene plays a role in retinoic acid-induced growth inhibition and differentiation of myeloid leukemia cells. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jan 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21042743).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASB2	NM_001202429.2	c.1572G>C	p.Arg524Ser	missense_variant	Exon 8 of 10	ENST00000555019.6	NP_001189358.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASB2	ENST00000555019.6	c.1572G>C	p.Arg524Ser	missense_variant	Exon 8 of 10	1	NM_001202429.2	ENSP00000451575.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000140 AC: 2 AN: 1426240 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 704398

Gnomad4 AFR exome AF: 0.0000619

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.: 32

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Uncertain	0.082	D
BayesDel_noAF	Benign	-0.12
CADD	Benign	20
DANN	Benign	0.83
DEOGEN2	Benign	0.033	.;T;.
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.66	D
M_CAP	Uncertain	0.18	D
MetaRNN	Benign	0.21	T;T;T
MetaSVM	Benign	-0.61	T
MutationAssessor	Uncertain	2.2	.;M;.
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.2	N;N;N
REVEL	Benign	0.24
Sift	Benign	0.57	T;T;T
Sift4G	Benign	0.50	T;T;.
Polyphen		0.067	.;B;.
Vest4		0.61
MutPred		0.34		.;Gain of glycosylation at R476 (P = 0.0115);.;
MVP		0.70
MPC		0.23
ClinPred		0.12	T
GERP RS		2.0
Varity_R		0.087
gMVP		0.72

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: rs540542265; hg19: chr14-94405499;