Variant 14-93939335-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001202429.2(ASB2):c.1390G>A(p.Gly464Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,458,674 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ASB2
NM_001202429.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.88

Variant links:

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]

ASB2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.764

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASB2	NM_001202429.2 linkuse as main transcript	c.1390G>A	p.Gly464Ser	missense_variant	8/10	ENST00000555019.6	NP_001189358.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASB2	ENST00000555019.6 linkuse as main transcript	c.1390G>A	p.Gly464Ser	missense_variant	8/10	1	NM_001202429.2	ENSP00000451575	P1	Q96Q27-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000404

AC:

AN:

247680

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134468

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000900

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1458674

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725302

show subpopulations

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:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000825

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 11, 2023

The c.1390G>A (p.G464S) alteration is located in exon 8 (coding exon 7) of the ASB2 gene. This alteration results from a G to A substitution at nucleotide position 1390, causing the glycine (G) at amino acid position 464 to be replaced by a serine (S). 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

Uncertain

0.42

BayesDel_addAF

Pathogenic

0.27

BayesDel_noAF

Pathogenic

0.15

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.47

.;T;.

Eigen

Pathogenic

0.83

Eigen_PC

Pathogenic

0.76

FATHMM_MKL

Pathogenic

0.99

M_CAP

Uncertain

0.18

MetaRNN

Pathogenic

0.76

D;D;D

MetaSVM

Uncertain

-0.23

MutationAssessor

Pathogenic

3.2

.;M;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.63

PROVEAN

Pathogenic

-5.4

D;D;D

REVEL

Uncertain

0.58

Sift

Pathogenic

0.0

D;D;D

Sift4G

Pathogenic

0.0

D;D;.

Polyphen

1.0

.;D;.

Vest4

0.78

MutPred

0.57

.;Gain of catalytic residue at L412 (P = 0.0095);.;

MVP

0.67

MPC

0.74

ClinPred

1.0

GERP RS

4.8

Varity_R

0.95

gMVP

0.89

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over