Genetic Variant SKA2:p.Ser39Arg (chr17-59131284-A-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_182620.4(SKA2):c.117T>G(p.Ser39Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SKA2
NM_182620.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.550

Publications

0 publications found

Variant links:

Genes affected

SKA2 (HGNC:28006): (spindle and kinetochore associated complex subunit 2) Enables microtubule binding activity. Involved in several processes, including chromosome segregation; mitotic cell cycle; and regulation of microtubule polymerization or depolymerization. Located in spindle microtubule. Part of outer kinetochore. [provided by Alliance of Genome Resources, Apr 2022]

SKA2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.103239596).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182620.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SKA2	NM_182620.4	MANE Select	c.117T>G	p.Ser39Arg	missense	Exon 2 of 4	NP_872426.1	Q8WVK7-1
SKA2	NM_001330399.2		c.117T>G	p.Ser39Arg	missense	Exon 2 of 4	NP_001317328.1	J3KSP0
SKA2	NM_001100595.2		c.212T>G	p.Val71Gly	missense	Exon 2 of 3	NP_001094065.1	Q8WVK7-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SKA2	ENST00000330137.12	TSL:1 MANE Select	c.117T>G	p.Ser39Arg	missense	Exon 2 of 4	ENSP00000333433.7	Q8WVK7-1
SKA2	ENST00000916133.1		c.111T>G	p.Ser37Arg	missense	Exon 2 of 4	ENSP00000586192.1
SKA2	ENST00000583380.5	TSL:5	c.117T>G	p.Ser39Arg	missense	Exon 2 of 4	ENSP00000462574.1	J3KSP0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1422324

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

704196

African (AFR)

AF:

0.00

AC:

AN:

32864

American (AMR)

AF:

0.00

AC:

AN:

39606

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25370

East Asian (EAS)

AF:

0.00

AC:

AN:

38632

South Asian (SAS)

AF:

0.00

AC:

AN:

80608

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51178

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5642

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1089606

Other (OTH)

AF:

0.00

AC:

AN:

58818

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.036

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.60

LIST_S2

Benign

0.69

M_CAP

Benign

0.025

MetaRNN

Benign

0.10

MetaSVM

Benign

-0.97

PhyloP100

0.55

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.4

REVEL

Benign

0.050

Sift

Benign

0.16

Sift4G

Benign

0.24

Polyphen

0.073

Vest4

0.16

MutPred

0.15

Loss of phosphorylation at S39 (P = 0.0594)

MVP

0.35

MPC

0.61

ClinPred

0.39

GERP RS

0.71

Varity_R

0.030

gMVP

0.15

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over