rs2281587

Variant names:

• chr10-103617592-C-T
• rs2281587
• NM_001394015.1:c.803-278G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001394015.1(SH3PXD2A):​c.803-278G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.295 in 152,186 control chromosomes in the GnomAD database, including 7,445 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 0.29 (7445 hom., cov: 33)
• Consequence: SH3PXD2A NM_001394015.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00700
• Publications: 4 publications found

Genes affected

SH3PXD2A (HGNC:23664): (SH3 and PX domains 2A) Predicted to enable superoxide-generating NADPH oxidase activator activity. Involved in osteoclast fusion and superoxide metabolic process. Located in podosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.505 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SH3PXD2A	NM_001394015.1	c.803-278G>A		intron_variant	Intron 10 of 14	ENST00000369774.9	NP_001380944.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SH3PXD2A	ENST00000369774.9	c.803-278G>A		intron_variant	Intron 10 of 14	5	NM_001394015.1	ENSP00000358789.4

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44872 AN: 152068 Hom.: 7444 Cov.: 33

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.207

Gnomad AMR AF: 0.337

Gnomad ASJ AF: 0.427

Gnomad EAS AF: 0.337

Gnomad SAS AF: 0.523

Gnomad FIN AF: 0.219

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.356

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.295 AC: 44881 AN: 152186 Hom.: 7445 Cov.: 33 AF XY: 0.296 AC XY: 21992 AN XY: 74414

African (AFR) AF: 0.167 AC: 6940 AN: 41528

American (AMR) AF: 0.337 AC: 5147 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.427 AC: 1482 AN: 3470

East Asian (EAS) AF: 0.336 AC: 1736 AN: 5166

South Asian (SAS) AF: 0.522 AC: 2519 AN: 4822

European-Finnish (FIN) AF: 0.219 AC: 2321 AN: 10618

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.348 AC: 23659 AN: 67970

Other (OTH) AF: 0.359 AC: 758 AN: 2114

Alfa AF: 0.314 Hom.: 981

Bravo AF: 0.293

Asia WGS AF: 0.462 AC: 1607 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.0
DANN	Benign	0.72
PhyloP100		0.0070
Mutation Taster		=100/0	polymorphism (auto)

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: rs2281587; hg19: chr10-105377349; COSMIC: COSV60116475;