ENST00000375286.7:n.*1379T>C – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000375286.7(KCTD2):n.*1379T>C variant causes a non coding transcript exon 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
ENST00000375286.7 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0910

Publications

29 publications found

Variant links:

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]

KCTD2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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	Effect	Exon rank	MANE	Protein	UniProt
KCTD2	NM_015353.3 link	c.*931T>C	3_prime_UTR_variant	Exon 6 of 6	ENST00000322444.7	NP_056168.1	Q14681Q8IYY2
KCTD2	NR_110834.2 link	n.1630T>C	non_coding_transcript_exon_variant	Exon 7 of 7
KCTD2	NR_110835.2 link	n.1749T>C	non_coding_transcript_exon_variant	Exon 8 of 8

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
KCTD2	ENST00000375286.7 link	n.*1379T>C	non_coding_transcript_exon_variant	Exon 7 of 7	1		ENSP00000364435.3	H0Y3B9
KCTD2	ENST00000322444.7 link	c.*931T>C	3_prime_UTR_variant	Exon 6 of 6	1	NM_015353.3	ENSP00000312814.6	Q14681
KCTD2	ENST00000375286.7 link	n.*1379T>C	3_prime_UTR_variant	Exon 7 of 7	1		ENSP00000364435.3	H0Y3B9

Frequencies

GnomAD3 genomes

AF:

0.245

AC:

37282

AN:

152074

Hom.:

7907

Cov.:

show subpopulations

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:

AN:

468

Hom.:

Cov.:

AF XY:

0.0816

AC XY:

AN XY:

294

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.0654

AC:

AN:

428

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0769

AC:

AN:

Other (OTH)

AF:

0.125

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.245

AC:

37330

AN:

152194

Hom.:

7916

Cov.:

AF XY:

0.247

AC XY:

18375

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.534

AC:

22143

AN:

41490

American (AMR)

AF:

0.170

AC:

2596

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.203

AC:

706

AN:

3472

East Asian (EAS)

AF:

0.619

AC:

3204

AN:

5172

South Asian (SAS)

AF:

0.324

AC:

1564

AN:

4820

European-Finnish (FIN)

AF:

0.0750

AC:

796

AN:

10616

Middle Eastern (MID)

AF:

0.235

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0835

AC:

5676

AN:

68008

Other (OTH)

AF:

0.199

AC:

421

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1119

2238

3358

4477

5596

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

354

708

1062

1416

1770

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.145

Hom.:

11211

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

(source)

DANN

Benign

0.75

PhyloP100

0.091

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over