Genetic Variant NM_182620.4:c.69A>G (chr17-59131332-T-C) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_ModerateBP6_ModerateBP7

The NM_182620.4(SKA2):c.69A>G(p.Gln23Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000335 in 1,580,746 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

SKA2
NM_182620.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.01

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.09465912).

BP6

Variant 17-59131332-T-C is Benign according to our data. Variant chr17-59131332-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3318687.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-2.01 with no splicing effect.

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.69A>G	p.Gln23Gln	synonymous	Exon 2 of 4	NP_872426.1	Q8WVK7-1
SKA2	NM_001100595.2		c.164A>G	p.Asn55Ser	missense	Exon 2 of 3	NP_001094065.1	Q8WVK7-2
SKA2	NM_001330399.2		c.69A>G	p.Gln23Gln	synonymous	Exon 2 of 4	NP_001317328.1	J3KSP0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SKA2	ENST00000330137.12	TSL:1 MANE Select	c.69A>G	p.Gln23Gln	synonymous	Exon 2 of 4	ENSP00000333433.7	Q8WVK7-1
SKA2	ENST00000437036.6	TSL:2	c.164A>G	p.Asn55Ser	missense	Exon 2 of 3	ENSP00000411231.2	Q8WVK7-2
SKA2	ENST00000916133.1		c.63A>G	p.Gln21Gln	synonymous	Exon 2 of 4	ENSP00000586192.1

Frequencies

GnomAD3 genomes

AF:

0.000118

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

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:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000385

AC:

AN:

207546

AF XY:

0.0000450

show subpopulations

Gnomad AFR exome

AF:

0.000157

Gnomad AMR exome

AF:

0.0000336

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000336

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000245

AC:

AN:

1428562

Hom.:

Cov.:

AF XY:

0.0000184

AC XY:

AN XY:

707698

show subpopulations

African (AFR)

AF:

0.000333

AC:

AN:

32988

American (AMR)

AF:

0.0000247

AC:

AN:

40560

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25462

East Asian (EAS)

AF:

0.0000257

AC:

AN:

38838

South Asian (SAS)

AF:

0.0000123

AC:

AN:

81380

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51518

Middle Eastern (MID)

AF:

0.000351

AC:

AN:

5704

European-Non Finnish (NFE)

AF:

0.0000156

AC:

AN:

1093072

Other (OTH)

AF:

0.0000339

AC:

AN:

59040

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.444

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000118

AC:

AN:

152184

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.000338

AC:

AN:

41454

American (AMR)

AF:

0.00

AC:

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5206

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68034

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000579

Hom.:

Bravo

AF:

0.000136

ESP6500AA

AF:

0.000547

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000167

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3472

ClinVar

ClinVar submissions

Significance:Likely benign

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

0.054

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.63

CADD

Benign

1.7

(source)

DANN

Benign

0.71

Eigen

Benign

-0.89

Eigen_PC

Benign

-0.87

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.40

M_CAP

Benign

0.0041

MetaRNN

Benign

0.095

MetaSVM

Benign

-0.97

PhyloP100

-2.0

PrimateAI

Benign

0.28

PROVEAN

Uncertain

-3.3

REVEL

Uncertain

0.37

Vest4

0.15

MVP

0.030

ClinPred

0.037

GERP RS

-3.5

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over