rs2467334

Positions:

• chr17-29808490-A-C
• chr17-29808490-A-G
• chr17-29808490-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001282129.2(SSH2):​c.145-14553T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.443 in 152,066 control chromosomes in the GnomAD database, including 15,316 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 0.44 (15316 hom., cov: 31)
• Consequence: SSH2 NM_001282129.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0400

Genes affected

SSH2 (HGNC:30580): (slingshot protein phosphatase 2) This gene encodes a protein tyrosine phosphatase that plays a key role in the regulation of actin filaments. The encoded protein dephosphorylates and activates cofilin, which promotes actin filament depolymerization. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.481 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SSH2	NM_001282129.2	c.145-14553T>G		intron_variant		ENST00000540801.6	NP_001269058.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SSH2	ENST00000540801.6	c.145-14553T>G		intron_variant		2	NM_001282129.2	ENSP00000444743	P4

Frequencies

GnomAD3 genomes AF: 0.443 AC: 67376 AN: 151948 Hom.: 15295 Cov.: 31

Gnomad AFR AF: 0.394

Gnomad AMI AF: 0.491

Gnomad AMR AF: 0.418

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.309

Gnomad SAS AF: 0.426

Gnomad FIN AF: 0.499

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.485

Gnomad OTH AF: 0.430

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

GnomAD4 genome AF: 0.443 AC: 67430 AN: 152066 Hom.: 15316 Cov.: 31 AF XY: 0.440 AC XY: 32688 AN XY: 74324

Gnomad4 AFR AF: 0.394

Gnomad4 AMR AF: 0.418

Gnomad4 ASJ AF: 0.382

Gnomad4 EAS AF: 0.308

Gnomad4 SAS AF: 0.427

Gnomad4 FIN AF: 0.499

Gnomad4 NFE AF: 0.485

Gnomad4 OTH AF: 0.434

Alfa AF: 0.365 Hom.: 1388

Bravo AF: 0.433

Asia WGS AF: 0.418 AC: 1453 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	9.7
DANN	Benign	0.77

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: rs2467334; hg19: chr17-28135508;