Genetic Variant SKA2:p.Leu26Leu (chr17-59131323-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP6_Moderate

The NM_001100595.2(SKA2):c.173G>A(p.Trp58*) variant causes a stop gained 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. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SKA2
NM_001100595.2 stop_gained

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.23

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;

BP6

Variant 17-59131323-C-T is Benign according to our data. Variant chr17-59131323-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3442263.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001100595.2. 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.78G>A	p.Leu26Leu	synonymous	Exon 2 of 4	NP_872426.1	Q8WVK7-1
SKA2	NM_001100595.2		c.173G>A	p.Trp58*	stop_gained	Exon 2 of 3	NP_001094065.1	Q8WVK7-2
SKA2	NM_001330399.2		c.78G>A	p.Leu26Leu	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.78G>A	p.Leu26Leu	synonymous	Exon 2 of 4	ENSP00000333433.7	Q8WVK7-1
SKA2	ENST00000437036.6	TSL:2	c.173G>A	p.Trp58*	stop_gained	Exon 2 of 3	ENSP00000411231.2	Q8WVK7-2
SKA2	ENST00000916133.1		c.72G>A	p.Leu24Leu	synonymous	Exon 2 of 4	ENSP00000586192.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000475

AC:

AN:

210324

AF XY:

0.00000887

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000110

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

6.99e-7

AC:

AN:

1429938

Hom.:

Cov.:

AF XY:

0.00000141

AC XY:

AN XY:

708514

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

33004

American (AMR)

AF:

0.00

AC:

AN:

40828

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25474

East Asian (EAS)

AF:

0.00

AC:

AN:

38844

South Asian (SAS)

AF:

0.00

AC:

AN:

81536

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51592

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5704

European-Non Finnish (NFE)

AF:

9.14e-7

AC:

AN:

1093858

Other (OTH)

AF:

0.00

AC:

AN:

59098

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

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

BayesDel_addAF

Benign

-0.095

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Uncertain

0.99

Eigen

Benign

-0.089

Eigen_PC

Benign

0.011

FATHMM_MKL

Uncertain

0.89

PhyloP100

3.2

Vest4

0.86

GERP RS

4.6

Mutation Taster

=71/129

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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