rs377071035

Variant names:

• chr9-2717754-T-A
• rs377071035
• NM_133497.4:c.15T>A

Your query was ambiguous. Multiple possible variants found:

• chr9-2717754-T-A
• chr9-2717754-T-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_133497.4(KCNV2):​c.15T>A​(p.Ser5Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000663 in 150,912 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S5S) has been classified as Likely benign.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
• Consequence: KCNV2 NM_133497.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.21
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06251186).

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.15T>A	p.Ser5Arg	missense	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.15T>A	p.Ser5Arg	missense	Exon 1 of 2	ENSP00000371514.3	Q8TDN2
	ENSG00000286670	ENST00000768783.1		n.113+28544A>T		intron	N/A
	ENSG00000286670	ENST00000768784.1		n.156+14191A>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00000663 AC: 1 AN: 150912 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000148

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 68

GnomAD4 genome AF: 0.00000663 AC: 1 AN: 150912 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 73588

African (AFR) AF: 0.00 AC: 0 AN: 40966

American (AMR) AF: 0.00 AC: 0 AN: 15202

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5114

South Asian (SAS) AF: 0.00 AC: 0 AN: 4748

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.0000148 AC: 1 AN: 67706

Other (OTH) AF: 0.00 AC: 0 AN: 2076

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Uncertain	0.029	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	0.082
DANN	Benign	0.96
DEOGEN2	Benign	0.056	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.059	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.063	T
MetaSVM	Uncertain	-0.058	T
MutationAssessor	Benign	1.8	L
PhyloP100		-2.2
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.16	N
REVEL	Benign	0.23
Sift	Uncertain	0.0020	D
Sift4G	Benign	0.35	T
Polyphen		0.0	B
Vest4		0.22
MutPred		0.25		Loss of phosphorylation at S5 (P = 0.0043)
MVP		0.56
MPC		0.019
ClinPred		0.066	T
GERP RS		-2.7
PromoterAI		0.048	Neutral
Varity_R		0.14
gMVP		0.24
Mutation Taster		=92/8	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: rs377071035; hg19: chr9-2717754;