17-59131314-T-C

Variant names:

• chr17-59131314-T-C
• NM_182620.4:c.87A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_001100595.2(SKA2):​c.182A>G​(p.Lys61Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 9/14 in silico tools predict 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 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.28

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 17-59131314-T-C is Benign according to our data. Variant chr17-59131314-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3442262.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SKA2	NM_182620.4	c.87A>G	p.Glu29Glu	synonymous_variant	Exon 2 of 4	ENST00000330137.12	NP_872426.1
SKA2	NM_001100595.2	c.182A>G	p.Lys61Arg	missense_variant	Exon 2 of 3		NP_001094065.1
SKA2	NM_001330399.2	c.87A>G	p.Glu29Glu	synonymous_variant	Exon 2 of 4		NP_001317328.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SKA2	ENST00000330137.12	c.87A>G	p.Glu29Glu	synonymous_variant	Exon 2 of 4	1	NM_182620.4	ENSP00000333433.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.99e-7 AC: 1 AN: 1430976 Hom.: 0 Cov.: 30 AF XY: 0.00000141 AC XY: 1 AN XY: 709024

Gnomad4 AFR exome AF: 0.00

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: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000169

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Oct 12, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	11
DANN	Uncertain	0.98
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.47	T
MetaSVM	Benign	-0.71	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.13
Vest4		0.59
MutPred		0.28		Loss of ubiquitination at K61 (P = 0.0362);
MVP		0.15
ClinPred		0.34	T
GERP RS		5.6

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: chr17-57208675;