rs7859993

Variant names:

• chr9-2718654-G-A
• rs7859993
• NM_133497.4:c.915G>A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_133497.4(KCNV2):​c.915G>A​(p.Val305Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0466 in 1,613,348 control chromosomes in the GnomAD database, including 1,976 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.043 (159 hom., cov: 33)
  • Exomes 𝑓: 0.047 (1817 hom.)
• Consequence: KCNV2 NM_133497.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.345
• Publications: 5 publications found

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]

KCNV2 Gene-Disease associations (from GenCC):

• cone dystrophy with supernormal rod response

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Labcorp Genetics (formerly Invitae)
• inherited retinal dystrophy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen

ENSG00000286670 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.031).
• BP6: Variant 9-2718654-G-A is Benign according to our data. Variant chr9-2718654-G-A is described in ClinVar as Benign. ClinVar VariationId is 262363.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.345 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0521 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_133497.4. 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
	KCNV2	NM_133497.4	MANE Select	c.915G>A	p.Val305Val	synonymous	Exon 1 of 2	NP_598004.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNV2	ENST00000382082.4	TSL:1 MANE Select	c.915G>A	p.Val305Val	synonymous	Exon 1 of 2	ENSP00000371514.3
	ENSG00000286670	ENST00000768783.1		n.113+27644C>T		intron	N/A
	ENSG00000286670	ENST00000768784.1		n.156+13291C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0429 AC: 6535 AN: 152194 Hom.: 159 Cov.: 33

Gnomad AFR AF: 0.0423

Gnomad AMI AF: 0.0804

Gnomad AMR AF: 0.0336

Gnomad ASJ AF: 0.0305

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0114

Gnomad FIN AF: 0.0303

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0536

Gnomad OTH AF: 0.0320

GnomAD2 exomes AF: 0.0353 AC: 8802 AN: 249330 AF XY: 0.0346

Gnomad AFR exome AF: 0.0421

Gnomad AMR exome AF: 0.0204

Gnomad ASJ exome AF: 0.0301

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0314

Gnomad NFE exome AF: 0.0520

Gnomad OTH exome AF: 0.0334

GnomAD4 exome AF: 0.0470 AC: 68719 AN: 1461036 Hom.: 1817 Cov.: 36 AF XY: 0.0459 AC XY: 33388 AN XY: 726876

African (AFR) AF: 0.0425 AC: 1423 AN: 33470

American (AMR) AF: 0.0221 AC: 989 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.0310 AC: 811 AN: 26122

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39692

South Asian (SAS) AF: 0.0129 AC: 1117 AN: 86256

European-Finnish (FIN) AF: 0.0331 AC: 1748 AN: 52786

Middle Eastern (MID) AF: 0.00520 AC: 30 AN: 5766

European-Non Finnish (NFE) AF: 0.0541 AC: 60157 AN: 1111852

Other (OTH) AF: 0.0404 AC: 2442 AN: 60376

GnomAD4 genome AF: 0.0429 AC: 6538 AN: 152312 Hom.: 159 Cov.: 33 AF XY: 0.0404 AC XY: 3009 AN XY: 74490

African (AFR) AF: 0.0422 AC: 1756 AN: 41584

American (AMR) AF: 0.0336 AC: 514 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0305 AC: 106 AN: 3472

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5160

South Asian (SAS) AF: 0.0114 AC: 55 AN: 4828

European-Finnish (FIN) AF: 0.0303 AC: 322 AN: 10622

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

European-Non Finnish (NFE) AF: 0.0536 AC: 3644 AN: 68020

Other (OTH) AF: 0.0317 AC: 67 AN: 2116

Alfa AF: 0.0489 Hom.: 535

Bravo AF: 0.0434

Asia WGS AF: 0.00693 AC: 24 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Cone dystrophy with supernormal rod response (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	7.9
DANN	Benign	0.89
PhyloP100		0.34
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: rs7859993; hg19: chr9-2718654; COSMIC: COSV66056463; COSMIC: COSV66056463;