Genetic Variant SSH2:p.Gly1339Ser (chr17-29631179-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001282129.2(SSH2):c.4015G>A(p.Gly1339Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00089 in 1,614,134 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0048 ( 13 hom., cov: 32)

Exomes 𝑓: 0.00049 ( 7 hom. )

Consequence

SSH2
NM_001282129.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.45

Variant links:

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]

SSH2 links:

ABHD15-AS1 (HGNC:49685): (ABHD15 antisense RNA 1)

ABHD15-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003778398).

BP6

Variant 17-29631179-C-T is Benign according to our data. Variant chr17-29631179-C-T is described in ClinVar as [Benign]. Clinvar id is 781362.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00477 (726/152282) while in subpopulation AFR AF= 0.0167 (692/41534). AF 95% confidence interval is 0.0156. There are 13 homozygotes in gnomad4. There are 320 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 726 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SSH2	NM_001282129.2 link	c.4015G>A	p.Gly1339Ser	missense_variant	Exon 16 of 16	ENST00000540801.6	NP_001269058.1	Q76I76F5H527B4DK64

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SSH2	ENST00000540801.6 link	c.4015G>A	p.Gly1339Ser	missense_variant	Exon 16 of 16	2	NM_001282129.2	ENSP00000444743.1		F5H527

Frequencies

GnomAD3 genomes

AF:

0.00478

AC:

727

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0167

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00164

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00127

AC:

320

AN:

251372

Hom.:

AF XY:

0.000920

AC XY:

125

AN XY:

135896

show subpopulations

Gnomad AFR exome

AF:

0.0183

Gnomad AMR exome

AF:

0.000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000486

AC:

710

AN:

1461852

Hom.:

Cov.:

AF XY:

0.000428

AC XY:

311

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.0176

Gnomad4 AMR exome

AF:

0.000760

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000279

Gnomad4 OTH exome

AF:

0.000894

GnomAD4 genome

AF:

0.00477

AC:

726

AN:

152282

Hom.:

Cov.:

AF XY:

0.00430

AC XY:

320

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.0167

Gnomad4 AMR

AF:

0.00163

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00332

Alfa

AF:

0.00227

Hom.:

Bravo

AF:

0.00556

ESP6500AA

AF:

0.0154

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00168

AC:

204

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 29, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.015

T;.;.

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.30

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.77

T;T;T

MetaRNN

Benign

0.0038

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

L;.;.

PrimateAI

Benign

0.26

PROVEAN

Benign

0.28

N;N;.

REVEL

Benign

0.093

Sift

Benign

0.23

T;T;.

Sift4G

Benign

0.82

T;T;.

Polyphen

0.0040

B;B;.

Vest4

0.060

MVP

0.37

MPC

0.083

ClinPred

0.0036

GERP RS

4.6

Varity_R

0.036

gMVP

0.11

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over