17-29630876-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001282129.2(SSH2):​c.4318A>G​(p.Lys1440Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

SSH2
NM_001282129.2 missense

Scores

3
8
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.01
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 Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.3210215).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SSH2NM_001282129.2 linkuse as main transcriptc.4318A>G p.Lys1440Glu 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.4318A>G p.Lys1440Glu missense_variant 16/162 NM_001282129.2 ENSP00000444743.1 F5H527

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

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 14, 2023The c.4237A>G (p.K1413E) alteration is located in exon 15 (coding exon 15) of the SSH2 gene. This alteration results from a A to G substitution at nucleotide position 4237, causing the lysine (K) at amino acid position 1413 to be replaced by a glutamic acid (E). 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
Pathogenic
0.57
BayesDel_addAF
Uncertain
0.059
T
BayesDel_noAF
Benign
-0.15
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.073
T;.;.
Eigen
Uncertain
0.63
Eigen_PC
Uncertain
0.66
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.88
D;D;D
M_CAP
Benign
0.013
T
MetaRNN
Benign
0.32
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.1
M;.;.
PrimateAI
Uncertain
0.70
T
PROVEAN
Benign
-0.97
N;N;.
REVEL
Benign
0.21
Sift
Uncertain
0.0010
D;D;.
Sift4G
Pathogenic
0.0
D;D;.
Polyphen
0.97
D;D;.
Vest4
0.34
MutPred
0.27
.;Loss of MoRF binding (P = 0.0073);.;
MVP
0.33
MPC
0.37
ClinPred
0.80
D
GERP RS
4.9
Varity_R
0.23
gMVP
0.43

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-27957894; API