chr9-2717676-T-G

Variant names:

• chr9-2717676-T-G
• rs11793555
• NM_133497.4:c.-64T>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_133497.4(KCNV2):​c.-64T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 1,604,192 control chromosomes in the GnomAD database, including 38,762 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (2718 hom., cov: 32)
  • Exomes 𝑓: 0.22 (36044 hom.)
• Consequence: KCNV2 NM_133497.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0490
• Publications: 11 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: G2P, Labcorp Genetics (formerly Invitae), Orphanet
• inherited retinal dystrophy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen

ENSG00000286670 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 9-2717676-T-G is Benign according to our data. Variant chr9-2717676-T-G is described in ClinVar as Benign. ClinVar VariationId is 366402.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.346 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.-64T>G		5_prime_UTR	Exon 1 of 2	NP_598004.1	Q8TDN2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNV2	ENST00000382082.4	TSL:1 MANE Select	c.-64T>G		5_prime_UTR	Exon 1 of 2	ENSP00000371514.3	Q8TDN2
	ENSG00000286670	ENST00000768783.1		n.113+28622A>C		intron	N/A
	ENSG00000286670	ENST00000768784.1		n.156+14269A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.175 AC: 26531 AN: 152012 Hom.: 2720 Cov.: 32

Gnomad AFR AF: 0.0708

Gnomad AMI AF: 0.239

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.242

Gnomad SAS AF: 0.360

Gnomad FIN AF: 0.208

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.205

GnomAD4 exome AF: 0.215 AC: 312813 AN: 1452062 Hom.: 36044 Cov.: 27 AF XY: 0.221 AC XY: 160141 AN XY: 723068

African (AFR) AF: 0.0658 AC: 2192 AN: 33302

American (AMR) AF: 0.145 AC: 6488 AN: 44678

Ashkenazi Jewish (ASJ) AF: 0.333 AC: 8680 AN: 26084

East Asian (EAS) AF: 0.258 AC: 10238 AN: 39644

South Asian (SAS) AF: 0.366 AC: 31319 AN: 85620

European-Finnish (FIN) AF: 0.202 AC: 10627 AN: 52714

Middle Eastern (MID) AF: 0.266 AC: 1521 AN: 5722

European-Non Finnish (NFE) AF: 0.207 AC: 228502 AN: 1104216

Other (OTH) AF: 0.220 AC: 13246 AN: 60082

GnomAD4 genome AF: 0.174 AC: 26522 AN: 152130 Hom.: 2718 Cov.: 32 AF XY: 0.177 AC XY: 13177 AN XY: 74360

African (AFR) AF: 0.0707 AC: 2938 AN: 41548

American (AMR) AF: 0.155 AC: 2365 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.323 AC: 1120 AN: 3468

East Asian (EAS) AF: 0.242 AC: 1245 AN: 5154

South Asian (SAS) AF: 0.360 AC: 1731 AN: 4810

European-Finnish (FIN) AF: 0.208 AC: 2196 AN: 10578

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.209 AC: 14192 AN: 67978

Other (OTH) AF: 0.206 AC: 434 AN: 2106

Alfa AF: 0.200 Hom.: 652

Bravo AF: 0.164

Asia WGS AF: 0.288 AC: 1000 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	1.6
DANN	Benign	0.74
PhyloP100		-0.049
PromoterAI		-0.023	Neutral
Mutation Taster		=145/155	disease causing

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: rs11793555; hg19: chr9-2717676; COSMIC: COSV66056360; COSMIC: COSV66056360;