rs7860945

chr9-2718717-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_133497.4(KCNV2):c.978C>T(p.Asp326=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0421 in 1,613,088 control chromosomes in the GnomAD database, including 1,599 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.046 (196 hom., cov: 33)
  • Exomes 𝑓: 0.042 (1403 hom.)
• Consequence: KCNV2 NM_133497.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.365

Genes affected

KCNV2 (HGNC:19698): (potassium voltage-gated channel modifier subfamily V member 2) Voltage-gated potassium (Kv) channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and cell volume. This gene encodes a member of the potassium voltage-gated channel subfamily V. This member is identified as a 'silent subunit', and it does not form homomultimers, but forms heteromultimers with several other subfamily members. Through obligatory heteromerization, it exerts a function-altering effect on other potassium channel subunits. This protein is strongly expressed in pancreas and has a weaker expression in several other tissues. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 9-2718717-C-T is Benign according to our data. Variant chr9-2718717-C-T is described in ClinVar as [Benign]. Clinvar id is 262364.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.365 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0608 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNV2	NM_133497.4	c.978C>T	p.Asp326=	synonymous_variant	1/2	ENST00000382082.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNV2	ENST00000382082.4	c.978C>T	p.Asp326=	synonymous_variant	1/2	1	NM_133497.4	P1

Frequencies

GnomAD3 genomes AF: 0.0460 AC: 6999 AN: 152228 Hom.: 196 Cov.: 33

Gnomad AFR AF: 0.0629

Gnomad AMI AF: 0.0800

Gnomad AMR AF: 0.0343

Gnomad ASJ AF: 0.0302

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0105

Gnomad FIN AF: 0.0291

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0478

Gnomad OTH AF: 0.0363

GnomAD3 exomes AF: 0.0344 AC: 8584 AN: 249466 Hom.: 209 AF XY: 0.0331 AC XY: 4475 AN XY: 135306

Gnomad AFR exome AF: 0.0647

Gnomad AMR exome AF: 0.0213

Gnomad ASJ exome AF: 0.0300

Gnomad EAS exome AF: 0.0000546

Gnomad SAS exome AF: 0.0118

Gnomad FIN exome AF: 0.0301

Gnomad NFE exome AF: 0.0472

Gnomad OTH exome AF: 0.0306

GnomAD4 exome AF: 0.0417 AC: 60972 AN: 1460742 Hom.: 1403 Cov.: 36 AF XY: 0.0408 AC XY: 29655 AN XY: 726764

Gnomad4 AFR exome AF: 0.0632

Gnomad4 AMR exome AF: 0.0230

Gnomad4 ASJ exome AF: 0.0306

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.0120

Gnomad4 FIN exome AF: 0.0314

Gnomad4 NFE exome AF: 0.0468

Gnomad4 OTH exome AF: 0.0372

GnomAD4 genome AF: 0.0460 AC: 7004 AN: 152346 Hom.: 196 Cov.: 33 AF XY: 0.0432 AC XY: 3216 AN XY: 74496

Gnomad4 AFR AF: 0.0628

Gnomad4 AMR AF: 0.0344

Gnomad4 ASJ AF: 0.0302

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.0106

Gnomad4 FIN AF: 0.0291

Gnomad4 NFE AF: 0.0478

Gnomad4 OTH AF: 0.0360

Alfa AF: 0.0465 Hom.: 129

Bravo AF: 0.0478

Asia WGS AF: 0.00751 AC: 26 AN: 3478

EpiCase AF: 0.0415

EpiControl AF: 0.0435

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Cone dystrophy with supernormal rod response Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
Cadd	Benign	6.4
Dann	Benign	0.93

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: rs7860945; hg19: chr9-2718717; COSMIC: COSV66056469; COSMIC: COSV66056469;