chr7-120273428-C-T

Position:

• chr7-120273428-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_012281.3(KCND2):​c.-1205C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0144 in 148,274 control chromosomes in the GnomAD database, including 55 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.014 (55 hom., cov: 32)
• Consequence: KCND2 NM_012281.3 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0980

Genes affected

KCND2 (HGNC:6238): (potassium voltage-gated channel subfamily D 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. Four sequence-related potassium channel genes - shaker, shaw, shab, and shal - have been identified in Drosophila, and each has been shown to have human homolog(s). This gene encodes a member of the potassium channel, voltage-gated, shal-related subfamily, members of which form voltage-activated A-type potassium ion channels and are prominent in the repolarization phase of the action potential. This member mediates a rapidly inactivating, A-type outward potassium current which is not under the control of the N terminus as it is in Shaker channels. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 7-120273428-C-T is Benign according to our data. Variant chr7-120273428-C-T is described in ClinVar as [Benign]. Clinvar id is 1277548.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0144 (2130/148274) while in subpopulation AFR AF= 0.0472 (1943/41128). AF 95% confidence interval is 0.0455. There are 55 homozygotes in gnomad4. There are 1023 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2130 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCND2	NM_012281.3	c.-1205C>T		5_prime_UTR_premature_start_codon_gain_variant	1/6	ENST00000331113.9	NP_036413.1
KCND2	NM_012281.3	c.-1205C>T		5_prime_UTR_variant	1/6	ENST00000331113.9	NP_036413.1
KCND2	XM_047420346.1	c.-1205C>T		5_prime_UTR_premature_start_codon_gain_variant	2/7		XP_047276302.1
KCND2	XM_047420346.1	c.-1205C>T		5_prime_UTR_variant	2/7		XP_047276302.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCND2	ENST00000331113	c.-1205C>T		5_prime_UTR_premature_start_codon_gain_variant	1/6	1	NM_012281.3	ENSP00000333496.4
KCND2	ENST00000331113	c.-1205C>T		5_prime_UTR_variant	1/6	1	NM_012281.3	ENSP00000333496.4

Frequencies

GnomAD3 genomes AF: 0.0143 AC: 2125 AN: 148170 Hom.: 54 Cov.: 32

Gnomad AFR AF: 0.0473

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00517

Gnomad ASJ AF: 0.00117

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0224

Gnomad NFE AF: 0.00114

Gnomad OTH AF: 0.00879

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0144 AC: 2130 AN: 148274 Hom.: 55 Cov.: 32 AF XY: 0.0141 AC XY: 1023 AN XY: 72298

Gnomad4 AFR AF: 0.0472

Gnomad4 AMR AF: 0.00516

Gnomad4 ASJ AF: 0.00117

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000831

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00114

Gnomad4 OTH AF: 0.00918

Alfa AF: 0.000647 Hom.: 0

Bravo AF: 0.0161

Asia WGS AF: 0.00758 AC: 26 AN: 3442

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 13, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.5
DANN	Benign	0.92

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs559392054; hg19: chr7-119913482;