17-59110368-G-A

Variant names:

• chr17-59110368-G-A
• rs7208505
• NM_182620.4:c.*1909C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_182620.4(SKA2):​c.*1909C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.639 in 151,986 control chromosomes in the GnomAD database, including 31,759 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.64 (31758 hom., cov: 31)
  • Exomes 𝑓: 1.0 (1 hom.)
• Consequence: SKA2 NM_182620.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.165
• Publications: 34 publications found

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]

ENSG00000224738 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.759 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SKA2	NM_182620.4	MANE Select	c.*1909C>T		3_prime_UTR	Exon 4 of 4	NP_872426.1
	SKA2	NM_001330399.2		c.*1965C>T		3_prime_UTR	Exon 4 of 4	NP_001317328.1
	SKA2	NM_001100595.2		c.*1965C>T		3_prime_UTR	Exon 3 of 3	NP_001094065.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SKA2	ENST00000330137.12	TSL:1 MANE Select	c.*1909C>T		3_prime_UTR	Exon 4 of 4	ENSP00000333433.7
	ENSG00000224738	ENST00000451775.3	TSL:2	n.994+2777G>A		intron	N/A
	ENSG00000224738	ENST00000722232.1		n.355+3038G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.639 AC: 96992 AN: 151866 Hom.: 31698 Cov.: 31

Gnomad AFR AF: 0.766

Gnomad AMI AF: 0.570

Gnomad AMR AF: 0.519

Gnomad ASJ AF: 0.592

Gnomad EAS AF: 0.396

Gnomad SAS AF: 0.579

Gnomad FIN AF: 0.639

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.614

Gnomad OTH AF: 0.630

GnomAD4 exome AF: 1.00 AC: 2 AN: 2 Hom.: 1 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 2 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.639 AC: 97105 AN: 151984 Hom.: 31758 Cov.: 31 AF XY: 0.638 AC XY: 47363 AN XY: 74272

African (AFR) AF: 0.767 AC: 31783 AN: 41464

American (AMR) AF: 0.519 AC: 7909 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.592 AC: 2052 AN: 3466

East Asian (EAS) AF: 0.396 AC: 2048 AN: 5172

South Asian (SAS) AF: 0.578 AC: 2791 AN: 4828

European-Finnish (FIN) AF: 0.639 AC: 6728 AN: 10534

Middle Eastern (MID) AF: 0.639 AC: 188 AN: 294

European-Non Finnish (NFE) AF: 0.614 AC: 41748 AN: 67960

Other (OTH) AF: 0.633 AC: 1338 AN: 2114

Alfa AF: 0.599 Hom.: 4535

Bravo AF: 0.627

Asia WGS AF: 0.525 AC: 1827 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.6
DANN	Benign	0.69
PhyloP100		-0.17
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7208505; hg19: chr17-57187729;