rs12943281

chr17-75033999-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000581589.5(KCTD2):c.-469-34G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0933 in 152,290 control chromosomes in the GnomAD database, including 1,477 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.093 (1477 hom., cov: 32)
  • Exomes 𝑓: 0.045 (0 hom.)
• Consequence: KCTD2 ENST00000581589.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.553

Genes affected

KCTD2 (HGNC:21294): (potassium channel tetramerization domain containing 2) Predicted to enable cullin family protein binding activity. Predicted to be involved in proteasome-mediated ubiquitin-dependent protein catabolic process. Predicted to be part of Cul3-RING ubiquitin ligase complex. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCTD2	NR_110835.2	n.155-34G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCTD2	ENST00000581589.5	c.-469-34G>A		intron_variant		1
KCTD2	ENST00000584767.5	n.501-34G>A		intron_variant, non_coding_transcript_variant		1
KCTD2	ENST00000579242.5	n.249-34G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0931 AC: 14164 AN: 152152 Hom.: 1471 Cov.: 32

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.00989

Gnomad AMR AF: 0.0416

Gnomad ASJ AF: 0.00662

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.00787

Gnomad FIN AF: 0.0298

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0312

Gnomad OTH AF: 0.0702

GnomAD4 exome AF: 0.0455 AC: 1 AN: 22 Hom.: 0 Cov.: 0 AF XY: 0.0625 AC XY: 1 AN XY: 16

Gnomad4 AFR exome AF: 0.167

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0933 AC: 14209 AN: 152268 Hom.: 1477 Cov.: 32 AF XY: 0.0896 AC XY: 6669 AN XY: 74470

Gnomad4 AFR AF: 0.263

Gnomad4 AMR AF: 0.0415

Gnomad4 ASJ AF: 0.00662

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.00787

Gnomad4 FIN AF: 0.0298

Gnomad4 NFE AF: 0.0312

Gnomad4 OTH AF: 0.0704

Alfa AF: 0.0661 Hom.: 120

Bravo AF: 0.102

Asia WGS AF: 0.0290 AC: 100 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
Cadd	Benign	1.9
Dann	Benign	0.54

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12943281; hg19: chr17-73030094;