7-120273428-C-T

Variant names:

• chr7-120273428-C-T
• rs559392054
• NM_012281.3:c.-1205C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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]

KCND2 Gene-Disease associations (from GenCC):

• KCND2-related neurodevelopmental disorder with or without seizures

  Inheritance: AD Classification: MODERATE Submitted by: G2P
• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Illumina

ENSG00000309549 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2130 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012281.3. 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
	KCND2	NM_012281.3	MANE Select	c.-1205C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 6	NP_036413.1	Q9NZV8
	KCND2	NM_012281.3	MANE Select	c.-1205C>T		5_prime_UTR	Exon 1 of 6	NP_036413.1	Q9NZV8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCND2	ENST00000331113.9	TSL:1 MANE Select	c.-1205C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 6	ENSP00000333496.4	Q9NZV8
	KCND2	ENST00000331113.9	TSL:1 MANE Select	c.-1205C>T		5_prime_UTR	Exon 1 of 6	ENSP00000333496.4	Q9NZV8
	ENSG00000309549	ENST00000841943.1		n.91+99G>A		intron	N/A

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

African (AFR) AF: 0.0472 AC: 1943 AN: 41128

American (AMR) AF: 0.00516 AC: 77 AN: 14920

Ashkenazi Jewish (ASJ) AF: 0.00117 AC: 4 AN: 3424

East Asian (EAS) AF: 0.00 AC: 0 AN: 5112

South Asian (SAS) AF: 0.000831 AC: 4 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9038

Middle Eastern (MID) AF: 0.0241 AC: 7 AN: 290

European-Non Finnish (NFE) AF: 0.00114 AC: 76 AN: 66564

Other (OTH) AF: 0.00918 AC: 19 AN: 2070

Alfa AF: 0.000647 Hom.: 0

Bravo AF: 0.0161

Asia WGS AF: 0.00758 AC: 26 AN: 3442

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.5
DANN	Benign	0.92
PhyloP100		-0.098
PromoterAI		-0.0038	Neutral

Splicing

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

Other links and lift over

dbSNP: rs559392054; hg19: chr7-119913482;