NM_001202429.2:c.1826G>C

Variant names:

• chr14-93934738-C-G
• rs905253804
• NM_001202429.2:c.1826G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001202429.2(ASB2):​c.1826G>C​(p.Gly609Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. G609V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ASB2 NM_001202429.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.59
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001202429.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASB2	NM_001202429.2	MANE Select	c.1826G>C	p.Gly609Ala	missense	Exon 10 of 10	NP_001189358.1	Q96Q27-2
	ASB2	NM_016150.5		c.1682G>C	p.Gly561Ala	missense	Exon 8 of 8	NP_057234.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASB2	ENST00000555019.6	TSL:1 MANE Select	c.1826G>C	p.Gly609Ala	missense	Exon 10 of 10	ENSP00000451575.1	Q96Q27-2
	ASB2	ENST00000315988.8	TSL:1	c.1682G>C	p.Gly561Ala	missense	Exon 8 of 8	ENSP00000320675.4	Q96Q27-1
	ASB2	ENST00000968954.1		c.1901G>C	p.Gly634Ala	missense	Exon 10 of 10	ENSP00000639013.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.67
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	T
Eigen	Pathogenic	0.72
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Pathogenic	0.98	D
M_CAP	Benign	0.055	D
MetaRNN	Uncertain	0.66	D
MetaSVM	Uncertain	-0.16	T
MutationAssessor	Uncertain	2.9	M
PhyloP100		3.6
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-4.2	D
REVEL	Uncertain	0.39
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.023	D
Polyphen		1.0	D
Vest4		0.54
MutPred		0.69		Gain of catalytic residue at K558 (P = 0.0338)
MVP		0.75
MPC		0.77
ClinPred		1.0	D
GERP RS		5.2
Varity_R		0.43
gMVP		0.85
Mutation Taster		=73/27	polymorphism

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

Other links and lift over

dbSNP: rs905253804; hg19: chr14-94401084;