10-124829420-G-A

Position:

• chr10-124829420-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_032182.4(ABRAXAS2):​c.606G>A​(p.Val202=) 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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABRAXAS2	NM_032182.4	c.606G>A	p.Val202=	synonymous_variant	7/9	ENST00000298492.6	NP_115558.3
ABRAXAS2	XM_047424888.1	c.294G>A	p.Val98=	synonymous_variant	6/8		XP_047280844.1
ABRAXAS2	XM_047424889.1	c.294G>A	p.Val98=	synonymous_variant	4/6		XP_047280845.1
ABRAXAS2	XM_047424891.1	c.294G>A	p.Val98=	synonymous_variant	4/6		XP_047280847.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABRAXAS2	ENST00000298492.6	c.606G>A	p.Val202=	synonymous_variant	7/9	1	NM_032182.4	ENSP00000298492	P1

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

GnomAD3 exomes AF: 0.564 AC: 140636 AN: 249308 Hom.: 41079 AF XY: 0.571 AC XY: 76982 AN XY: 134840

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 SAS exome AF: 0.618

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

Gnomad4 AFR exome AF: 0.205

Gnomad4 AMR exome AF: 0.609

Gnomad4 ASJ exome AF: 0.663

Gnomad4 EAS exome AF: 0.628

Gnomad4 SAS exome AF: 0.613

Gnomad4 FIN exome AF: 0.598

Gnomad4 NFE exome AF: 0.570

Gnomad4 OTH exome AF: 0.555

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

Gnomad4 AFR AF: 0.224

Gnomad4 AMR AF: 0.596

Gnomad4 ASJ AF: 0.645

Gnomad4 EAS AF: 0.596

Gnomad4 SAS AF: 0.642

Gnomad4 FIN AF: 0.603

Gnomad4 NFE AF: 0.573

Gnomad4 OTH AF: 0.508

Alfa AF: 0.549 Hom.: 30004

Bravo AF: 0.470

Asia WGS AF: 0.593 AC: 2058 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.84
DANN	Benign	0.68

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

Other links and lift over

dbSNP: rs2303611; hg19: chr10-126517989; COSMIC: COSV53717012;