10-124829420-G-A

Variant names:

• chr10-124829420-G-A
• rs2303611
• NM_032182.4:c.606G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_032182.4(ABRAXAS2):​c.606G>A​(p.Val202Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.561 in 1,605,338 control chromosomes in the GnomAD database, including 259,381 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.48 (19927 hom., cov: 32)
  • Exomes 𝑓: 0.57 (239454 hom.)
• Consequence: ABRAXAS2 NM_032182.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.00
• Publications: 30 publications found

Genes affected

ABRAXAS2 (HGNC:28975): (abraxas 2, BRISC complex subunit) Enables microtubule binding activity and polyubiquitin modification-dependent protein binding activity. Involved in several processes, including mitotic spindle assembly; protein K63-linked deubiquitination; and response to ischemia. Located in cytoplasm. Part of BRISC complex. Colocalizes with microtubule minus-end; midbody; and spindle pole centrosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP7: Synonymous conserved (PhyloP=-1 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.623 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032182.4. 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
	ABRAXAS2	NM_032182.4	MANE Select	c.606G>A	p.Val202Val	synonymous	Exon 7 of 9	NP_115558.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABRAXAS2	ENST00000298492.6	TSL:1 MANE Select	c.606G>A	p.Val202Val	synonymous	Exon 7 of 9	ENSP00000298492.5
	ABRAXAS2	ENST00000899981.1		c.1011G>A	p.Val337Val	synonymous	Exon 7 of 9	ENSP00000570040.1
	ABRAXAS2	ENST00000899980.1		c.498G>A	p.Val166Val	synonymous	Exon 5 of 7	ENSP00000570039.1

Frequencies

GnomAD3 genomes AF: 0.485 AC: 73641 AN: 151930 Hom.: 19907 Cov.: 32

Gnomad AFR AF: 0.225

Gnomad AMI AF: 0.356

Gnomad AMR AF: 0.596

Gnomad ASJ AF: 0.645

Gnomad EAS AF: 0.596

Gnomad SAS AF: 0.641

Gnomad FIN AF: 0.603

Gnomad MID AF: 0.548

Gnomad NFE AF: 0.573

Gnomad OTH AF: 0.502

GnomAD2 exomes AF: 0.564 AC: 140636 AN: 249308 AF XY: 0.571

Gnomad AFR exome AF: 0.217

Gnomad AMR exome AF: 0.611

Gnomad ASJ exome AF: 0.668

Gnomad EAS exome AF: 0.591

Gnomad FIN exome AF: 0.605

Gnomad NFE exome AF: 0.564

Gnomad OTH exome AF: 0.565

GnomAD4 exome AF: 0.569 AC: 827324 AN: 1453290 Hom.: 239454 Cov.: 32 AF XY: 0.571 AC XY: 413198 AN XY: 723318

African (AFR) AF: 0.205 AC: 6827 AN: 33294

American (AMR) AF: 0.609 AC: 26836 AN: 44046

Ashkenazi Jewish (ASJ) AF: 0.663 AC: 17277 AN: 26048

East Asian (EAS) AF: 0.628 AC: 24846 AN: 39568

South Asian (SAS) AF: 0.613 AC: 52488 AN: 85582

European-Finnish (FIN) AF: 0.598 AC: 31911 AN: 53376

Middle Eastern (MID) AF: 0.553 AC: 3181 AN: 5750

European-Non Finnish (NFE) AF: 0.570 AC: 630592 AN: 1105550

Other (OTH) AF: 0.555 AC: 33366 AN: 60076

GnomAD4 genome AF: 0.485 AC: 73679 AN: 152048 Hom.: 19927 Cov.: 32 AF XY: 0.493 AC XY: 36604 AN XY: 74316

African (AFR) AF: 0.224 AC: 9312 AN: 41490

American (AMR) AF: 0.596 AC: 9096 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.645 AC: 2238 AN: 3472

East Asian (EAS) AF: 0.596 AC: 3080 AN: 5168

South Asian (SAS) AF: 0.642 AC: 3091 AN: 4818

European-Finnish (FIN) AF: 0.603 AC: 6369 AN: 10554

Middle Eastern (MID) AF: 0.548 AC: 160 AN: 292

European-Non Finnish (NFE) AF: 0.573 AC: 38939 AN: 67980

Other (OTH) AF: 0.508 AC: 1070 AN: 2106

Alfa AF: 0.540 Hom.: 36262

Bravo AF: 0.470

Asia WGS AF: 0.593 AC: 2058 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.84
DANN	Benign	0.68
PhyloP100		-1.0
Mutation Taster		=56/44	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: rs2303611; hg19: chr10-126517989; COSMIC: COSV53717012;