14-93937775-C-T

Variant names:

• chr14-93937775-C-T
• NM_001202429.2:c.1694G>A

Variant summary

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

The NM_001202429.2(ASB2):​c.1694G>A​(p.Gly565Asp) 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)
• Consequence: ASB2 NM_001202429.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.08

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 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
ASB2	NM_001202429.2	c.1694G>A	p.Gly565Asp	missense_variant	Exon 9 of 10	ENST00000555019.6	NP_001189358.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASB2	ENST00000555019.6	c.1694G>A	p.Gly565Asp	missense_variant	Exon 9 of 10	1	NM_001202429.2	ENSP00000451575.1
ASB2	ENST00000315988.8	c.1550G>A	p.Gly517Asp	missense_variant	Exon 7 of 8	1		ENSP00000320675.4
ASB2	ENST00000555507.5	c.1388G>A	p.Gly463Asp	missense_variant	Exon 7 of 7	5		ENSP00000450940.1
ASB2	ENST00000553883.1	n.1465G>A		non_coding_transcript_exon_variant	Exon 2 of 3	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 09, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1694G>A (p.G565D) alteration is located in exon 9 (coding exon 8) of the ASB2 gene. This alteration results from a G to A substitution at nucleotide position 1694, causing the glycine (G) at amino acid position 565 to be replaced by an aspartic acid (D). 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	0.93
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.036	.;T;.
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.85	D
M_CAP	Benign	0.045	D
MetaRNN	Uncertain	0.43	T;T;T
MetaSVM	Benign	-0.61	T
MutationAssessor	Benign	1.9	.;L;.
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-0.26	N;N;N
REVEL	Benign	0.28
Sift	Benign	0.48	T;T;T
Sift4G	Benign	0.11	T;T;.
Polyphen		1.0	.;D;.
Vest4		0.83
MutPred		0.59		.;Gain of catalytic residue at L513 (P = 2e-04);.;
MVP		0.72
MPC		0.85
ClinPred		0.73	D
GERP RS		5.1
Varity_R		0.29
gMVP		0.92

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: chr14-94404121;