rs11870474

Positions:

• chr17-75034715-C-A
• chr17-75034715-C-T

Variant summary

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

The ENST00000581589.5(KCTD2):​c.-384-517C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0924 in 152,008 control chromosomes in the GnomAD database, including 1,518 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 0.092 (1518 hom., cov: 32)
• Consequence: KCTD2 ENST00000581589.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.73

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=-0.73).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.263 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCTD2	NR_110835.2	n.240-517C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCTD2	ENST00000581589.5	c.-384-517C>A		intron_variant		1
KCTD2	ENST00000584767.5	n.586-517C>A		intron_variant, non_coding_transcript_variant		1
KCTD2	ENST00000579242.5	n.334-517C>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0922 AC: 14003 AN: 151892 Hom.: 1513 Cov.: 32

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.00659

Gnomad AMR AF: 0.0413

Gnomad ASJ AF: 0.00634

Gnomad EAS AF: 0.00136

Gnomad SAS AF: 0.00789

Gnomad FIN AF: 0.0215

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0280

Gnomad OTH AF: 0.0677

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

GnomAD4 genome AF: 0.0924 AC: 14048 AN: 152008 Hom.: 1518 Cov.: 32 AF XY: 0.0885 AC XY: 6575 AN XY: 74330

Gnomad4 AFR AF: 0.267

Gnomad4 AMR AF: 0.0412

Gnomad4 ASJ AF: 0.00634

Gnomad4 EAS AF: 0.00136

Gnomad4 SAS AF: 0.00790

Gnomad4 FIN AF: 0.0215

Gnomad4 NFE AF: 0.0280

Gnomad4 OTH AF: 0.0680

Alfa AF: 0.0288 Hom.: 225

Bravo AF: 0.102

Asia WGS AF: 0.0300 AC: 103 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.17
DANN	Benign	0.50

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11870474; hg19: chr17-73030810;