NM_001202429.2:c.1577A>G

Variant names:

• chr14-93939148-T-C
• rs368927735
• NM_001202429.2:c.1577A>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001202429.2(ASB2):​c.1577A>G​(p.Asn526Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000152 in 1,573,786 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00016 (1 hom.)
• Consequence: ASB2 NM_001202429.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.156
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.009416312).
• BP6: Variant 14-93939148-T-C is Benign according to our data. Variant chr14-93939148-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3130166.Status of the report is criteria_provided_single_submitter, 1 stars.

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.1577A>G	p.Asn526Ser	missense	Exon 8 of 10	NP_001189358.1	Q96Q27-2
	ASB2	NM_016150.5		c.1433A>G	p.Asn478Ser	missense	Exon 6 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.1577A>G	p.Asn526Ser	missense	Exon 8 of 10	ENSP00000451575.1	Q96Q27-2
	ASB2	ENST00000315988.8	TSL:1	c.1433A>G	p.Asn478Ser	missense	Exon 6 of 8	ENSP00000320675.4	Q96Q27-1
	ASB2	ENST00000968954.1		c.1652A>G	p.Asn551Ser	missense	Exon 8 of 10	ENSP00000639013.1

Frequencies

GnomAD3 genomes AF: 0.000118 AC: 18 AN: 152164 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000174 AC: 36 AN: 207112 AF XY: 0.000236

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000638

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000188

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000155 AC: 221 AN: 1421622 Hom.: 1 Cov.: 31 AF XY: 0.000180 AC XY: 126 AN XY: 701560

African (AFR) AF: 0.0000311 AC: 1 AN: 32176

American (AMR) AF: 0.0000248 AC: 1 AN: 40262

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25160

East Asian (EAS) AF: 0.0000260 AC: 1 AN: 38484

South Asian (SAS) AF: 0.000793 AC: 66 AN: 83250

European-Finnish (FIN) AF: 0.0000199 AC: 1 AN: 50308

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5240

European-Non Finnish (NFE) AF: 0.000135 AC: 147 AN: 1088298

Other (OTH) AF: 0.0000684 AC: 4 AN: 58444

GnomAD4 genome AF: 0.000118 AC: 18 AN: 152164 Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11 AN XY: 74334

African (AFR) AF: 0.00 AC: 0 AN: 41438

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00103 AC: 5 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000108 Hom.: 0

Bravo AF: 0.0000793

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000121 AC: 1

ExAC AF: 0.000210 AC: 25

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.056
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	7.5
DANN	Benign	0.71
DEOGEN2	Benign	0.019	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.73	D
M_CAP	Benign	0.073	D
MetaRNN	Benign	0.0094	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.16
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.40	N
REVEL	Benign	0.045
Sift	Benign	0.62	T
Sift4G	Benign	0.61	T
Polyphen		0.0	B
Vest4		0.053
MVP		0.37
MPC		0.15
ClinPred		0.016	T
GERP RS		-2.5
Varity_R		0.026
gMVP		0.54
Mutation Taster		=98/2	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: rs368927735; hg19: chr14-94405494;