chr17-29631398-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_001282129.2(SSH2):​c.3796G>A​(p.Glu1266Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000489 in 1,613,998 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000053 ( 0 hom. )

Consequence

SSH2
NM_001282129.2 missense

Scores

2
8
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.31
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.28365475).
BS2
High AC in GnomAdExome4 at 77 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SSH2NM_001282129.2 linkuse as main transcriptc.3796G>A p.Glu1266Lys missense_variant 16/16 ENST00000540801.6 NP_001269058.1 Q76I76F5H527B4DK64

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SSH2ENST00000540801.6 linkuse as main transcriptc.3796G>A p.Glu1266Lys missense_variant 16/162 NM_001282129.2 ENSP00000444743.1 F5H527

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152112
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.00
GnomAD3 exomes
AF:
0.0000159
AC:
4
AN:
251334
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135860
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000462
Gnomad NFE exome
AF:
0.0000264
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000527
AC:
77
AN:
1461886
Hom.:
0
Cov.:
31
AF XY:
0.0000371
AC XY:
27
AN XY:
727244
show subpopulations
Gnomad4 AFR exome
AF:
0.0000597
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.0000647
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152112
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74306
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
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:
0.00
Alfa
AF:
0.0000564
Hom.:
0
Bravo
AF:
0.00000756
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.0000545
EpiControl
AF:
0.000119

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJul 20, 2022The c.3715G>A (p.E1239K) alteration is located in exon 15 (coding exon 15) of the SSH2 gene. This alteration results from a G to A substitution at nucleotide position 3715, causing the glutamic acid (E) at amino acid position 1239 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.15
BayesDel_addAF
Pathogenic
0.17
D
BayesDel_noAF
Uncertain
0.070
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Benign
0.10
T;.;.
Eigen
Uncertain
0.52
Eigen_PC
Uncertain
0.51
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.88
D;D;D
M_CAP
Benign
0.021
T
MetaRNN
Benign
0.28
T;T;T
MetaSVM
Benign
-0.97
T
MutationAssessor
Uncertain
2.2
M;.;.
PrimateAI
Benign
0.45
T
PROVEAN
Benign
-1.9
N;N;.
REVEL
Benign
0.25
Sift
Uncertain
0.0010
D;D;.
Sift4G
Uncertain
0.0060
D;D;.
Polyphen
0.99
D;D;.
Vest4
0.38
MutPred
0.35
.;Gain of MoRF binding (P = 0.0044);.;
MVP
0.64
MPC
0.10
ClinPred
0.59
D
GERP RS
5.2
Varity_R
0.21
gMVP
0.62

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.

Other links and lift over

dbSNP: rs745762993; hg19: chr17-27958416; API