NM_015353.3:c.44G>A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_015353.3(KCTD2):c.44G>A(p.Gly15Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000397 in 151,116 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000040 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000020 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

KCTD2
NM_015353.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.345

Publications

0 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:

ATP5PD (HGNC:845): (ATP synthase peripheral stalk subunit d) Mitochondrial ATP synthase catalyzes ATP synthesis, utilizing an electrochemical gradient of protons across the inner membrane during oxidative phosphorylation. It is composed of two linked multi-subunit complexes: the soluble catalytic core, F1, and the membrane-spanning component, Fo, which comprises the proton channel. The F1 complex consists of 5 different subunits (alpha, beta, gamma, delta, and epsilon) assembled in a ratio of 3 alpha, 3 beta, and a single representative of the other 3. The Fo seems to have nine subunits (a, b, c, d, e, f, g, F6 and 8). This gene encodes the d subunit of the Fo complex. Alternatively spliced transcript variants encoding different isoforms have been identified for this gene. In addition, three pseudogenes are located on chromosomes 9, 12 and 15. [provided by RefSeq, Jun 2010]

ATP5PD links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.08530247).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015353.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KCTD2	NM_015353.3	MANE Select	c.44G>A	p.Gly15Glu	missense	Exon 1 of 6	NP_056168.1	Q14681
KCTD2	NR_110834.2		n.70G>A		non_coding_transcript_exon	Exon 1 of 7
KCTD2	NR_110835.2		n.366-1926G>A		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KCTD2	ENST00000322444.7	TSL:1 MANE Select	c.44G>A	p.Gly15Glu	missense	Exon 1 of 6	ENSP00000312814.6	Q14681
KCTD2	ENST00000581589.5	TSL:1	c.-258-1926G>A		intron	N/A	ENSP00000464630.1	J3QSC8
KCTD2	ENST00000375286.7	TSL:1	n.44G>A		non_coding_transcript_exon	Exon 1 of 7	ENSP00000364435.3	H0Y3B9

Frequencies

GnomAD3 genomes

AF:

0.0000397

AC:

AN:

151008

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00117

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000198

AC:

AN:

1008996

Hom.:

Cov.:

AF XY:

0.00000209

AC XY:

AN XY:

477764

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

20786

American (AMR)

AF:

0.00

AC:

AN:

6518

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

11890

East Asian (EAS)

AF:

0.0000457

AC:

AN:

21864

South Asian (SAS)

AF:

0.00

AC:

AN:

21424

European-Finnish (FIN)

AF:

0.00

AC:

AN:

17972

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2582

European-Non Finnish (NFE)

AF:

0.00000115

AC:

AN:

866958

Other (OTH)

AF:

0.00

AC:

AN:

39002

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000397

AC:

AN:

151116

Hom.:

Cov.:

AF XY:

0.0000406

AC XY:

AN XY:

73864

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41418

American (AMR)

AF:

0.00

AC:

AN:

15192

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00117

AC:

AN:

5124

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10082

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67710

Other (OTH)

AF:

0.00

AC:

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.0000567

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.039

BayesDel_noAF

Benign

-0.29

CADD

Benign

(source)

DANN

Benign

0.87

DEOGEN2

Benign

0.0044

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.53

FATHMM_MKL

Benign

0.46

LIST_S2

Benign

0.51

M_CAP

Pathogenic

0.78

MetaRNN

Benign

0.085

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

PhyloP100

0.34

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

-0.71

REVEL

Benign

0.10

Sift

Benign

0.99

Sift4G

Benign

0.87

Polyphen

0.0010

Vest4

0.29

MutPred

0.26

Gain of solvent accessibility (P = 0.0789)

MVP

0.47

MPC

1.3

ClinPred

0.22

GERP RS

-1.4

PromoterAI

0.11

Neutral

(source)

Varity_R

0.081

gMVP

0.22

Mutation Taster

=91/9

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over