rs7208505

Positions:

• chr17-59110368-G-A
• chr17-59110368-G-C
• chr17-59110368-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000330137.12(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 ENST00000330137.12 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.165

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SKA2	NM_182620.4	c.*1909C>T		3_prime_UTR_variant	4/4	ENST00000330137.12	NP_872426.1
LOC124904039	XR_007065864.1	n.496+2777G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SKA2	ENST00000330137.12	c.*1909C>T		3_prime_UTR_variant	4/4	1	NM_182620.4	ENSP00000333433	P1
	ENST00000451775.2	n.994+2777G>A		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 NFE exome AF: 1.00

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

Gnomad4 AFR AF: 0.767

Gnomad4 AMR AF: 0.519

Gnomad4 ASJ AF: 0.592

Gnomad4 EAS AF: 0.396

Gnomad4 SAS AF: 0.578

Gnomad4 FIN AF: 0.639

Gnomad4 NFE AF: 0.614

Gnomad4 OTH AF: 0.633

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.6
DANN	Benign	0.69

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

LitVar

Other links and lift over

dbSNP: rs7208505; hg19: chr17-57187729;