8-98428975-C-T

Variant names:

• chr8-98428975-C-T
• rs145439108
• NM_020697.4:c.996C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_020697.4(KCNS2):​c.996C>T​(p.Leu332Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0042 in 1,614,170 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0034 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0043 (18 hom.)
• Consequence: KCNS2 NM_020697.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.03
• Publications: 1 publications found

Genes affected

KCNS2 (HGNC:6301): (potassium voltage-gated channel modifier subfamily S member 2) Predicted to enable voltage-gated potassium channel activity. Predicted to be involved in potassium ion transmembrane transport and regulation of delayed rectifier potassium channel activity. Predicted to be located in perinuclear region of cytoplasm and plasma membrane. Predicted to be part of voltage-gated potassium channel complex. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

STK3 (HGNC:11406): (serine/threonine kinase 3) This gene encodes a serine/threonine protein kinase activated by proapoptotic molecules indicating the encoded protein functions as a growth suppressor. Cleavage of the protein product by caspase removes the inhibitory C-terminal portion. The N-terminal portion is transported to the nucleus where it homodimerizes to form the active kinase which promotes the condensation of chromatin during apoptosis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 8-98428975-C-T is Benign according to our data. Variant chr8-98428975-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3387888.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.03 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 18 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020697.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNS2	NM_020697.4	MANE Select	c.996C>T	p.Leu332Leu	synonymous	Exon 2 of 2	NP_065748.1	Q9ULS6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNS2	ENST00000287042.5	TSL:1 MANE Select	c.996C>T	p.Leu332Leu	synonymous	Exon 2 of 2	ENSP00000287042.4	Q9ULS6
	KCNS2	ENST00000521839.1	TSL:5	c.996C>T	p.Leu332Leu	synonymous	Exon 2 of 2	ENSP00000430712.1	Q9ULS6
	STK3	ENST00000517832.1	TSL:3	n.483+5152G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00338 AC: 515 AN: 152188 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00123

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00281

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00471

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00519

Gnomad OTH AF: 0.00335

GnomAD2 exomes AF: 0.00324 AC: 814 AN: 251236 AF XY: 0.00331

Gnomad AFR exome AF: 0.000862

Gnomad AMR exome AF: 0.00257

Gnomad ASJ exome AF: 0.0000993

Gnomad EAS exome AF: 0.000218

Gnomad FIN exome AF: 0.00504

Gnomad NFE exome AF: 0.00460

Gnomad OTH exome AF: 0.00392

GnomAD4 exome AF: 0.00429 AC: 6267 AN: 1461864 Hom.: 18 Cov.: 32 AF XY: 0.00414 AC XY: 3008 AN XY: 727230

African (AFR) AF: 0.000747 AC: 25 AN: 33480

American (AMR) AF: 0.00253 AC: 113 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26136

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39700

South Asian (SAS) AF: 0.00204 AC: 176 AN: 86256

European-Finnish (FIN) AF: 0.00391 AC: 209 AN: 53396

Middle Eastern (MID) AF: 0.00104 AC: 6 AN: 5768

European-Non Finnish (NFE) AF: 0.00497 AC: 5522 AN: 1112008

Other (OTH) AF: 0.00349 AC: 211 AN: 60396

GnomAD4 genome AF: 0.00338 AC: 515 AN: 152306 Hom.: 0 Cov.: 32 AF XY: 0.00325 AC XY: 242 AN XY: 74480

African (AFR) AF: 0.00123 AC: 51 AN: 41574

American (AMR) AF: 0.00281 AC: 43 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5168

South Asian (SAS) AF: 0.00166 AC: 8 AN: 4816

European-Finnish (FIN) AF: 0.00471 AC: 50 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00519 AC: 353 AN: 68030

Other (OTH) AF: 0.00331 AC: 7 AN: 2112

Alfa AF: 0.00398 Hom.: 0

Bravo AF: 0.00308

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00409

EpiControl AF: 0.00504

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	5.7
DANN	Benign	0.84
PhyloP100		1.0
Mutation Taster		=100/0	polymorphism

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: rs145439108; hg19: chr8-99441203;