chr17-75063978-T-C

Position:

• chr17-75063978-T-C

Variant summary

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

The ENST00000322444.7(KCTD2):​c.*931T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 152,662 control chromosomes in the GnomAD database, including 7,918 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 0.25 (7916 hom., cov: 32)
  • Exomes 𝑓: 0.071 (2 hom.)
• Consequence: KCTD2 ENST00000322444.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0910

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.602 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCTD2	NM_015353.3	c.*931T>C		3_prime_UTR_variant	6/6	ENST00000322444.7	NP_056168.1
KCTD2	NR_110834.2	n.1630T>C		non_coding_transcript_exon_variant	7/7
KCTD2	NR_110835.2	n.1749T>C		non_coding_transcript_exon_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCTD2	ENST00000322444.7	c.*931T>C		3_prime_UTR_variant	6/6	1	NM_015353.3	ENSP00000312814	P1
KCTD2	ENST00000375286.7	c.*1379T>C		3_prime_UTR_variant, NMD_transcript_variant	7/7	1		ENSP00000364435

Frequencies

GnomAD3 genomes AF: 0.245 AC: 37282 AN: 152074 Hom.: 7907 Cov.: 32

Gnomad AFR AF: 0.534

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.203

Gnomad EAS AF: 0.620

Gnomad SAS AF: 0.323

Gnomad FIN AF: 0.0750

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.0835

Gnomad OTH AF: 0.202

GnomAD4 exome AF: 0.0705 AC: 33 AN: 468 Hom.: 2 Cov.: 0 AF XY: 0.0816 AC XY: 24 AN XY: 294

Gnomad4 AFR exome AF: 0.00

Gnomad4 EAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.0654

Gnomad4 NFE exome AF: 0.0769

Gnomad4 OTH exome AF: 0.125

GnomAD4 genome AF: 0.245 AC: 37330 AN: 152194 Hom.: 7916 Cov.: 32 AF XY: 0.247 AC XY: 18375 AN XY: 74424

Gnomad4 AFR AF: 0.534

Gnomad4 AMR AF: 0.170

Gnomad4 ASJ AF: 0.203

Gnomad4 EAS AF: 0.619

Gnomad4 SAS AF: 0.324

Gnomad4 FIN AF: 0.0750

Gnomad4 NFE AF: 0.0835

Gnomad4 OTH AF: 0.199

Alfa AF: 0.116 Hom.: 4369

Bravo AF: 0.269

Asia WGS AF: 0.404 AC: 1403 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.9
DANN	Benign	0.75
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

Publications

LitVar

Other links and lift over

dbSNP: rs11077773; hg19: chr17-73060073;