Genetic Variant NM_015353.3:c.7G>A (chr17-75047257-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015353.3(KCTD2):c.7G>A(p.Glu3Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E3D) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 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: 5.21

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2304421).

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.7G>A	p.Glu3Lys	missense	Exon 1 of 6	NP_056168.1	Q14681
KCTD2	NR_110834.2		n.33G>A		non_coding_transcript_exon	Exon 1 of 7
KCTD2	NR_110835.2		n.366-1963G>A		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KCTD2	ENST00000322444.7	TSL:1 MANE Select	c.7G>A	p.Glu3Lys	missense	Exon 1 of 6	ENSP00000312814.6	Q14681
KCTD2	ENST00000581589.5	TSL:1	c.-258-1963G>A		intron	N/A	ENSP00000464630.1	J3QSC8
KCTD2	ENST00000375286.7	TSL:1	n.7G>A		non_coding_transcript_exon	Exon 1 of 7	ENSP00000364435.3	H0Y3B9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

704218

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

335050

African (AFR)

AF:

0.00

AC:

AN:

12998

American (AMR)

AF:

0.00

AC:

AN:

2464

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

5592

East Asian (EAS)

AF:

0.00

AC:

AN:

5286

South Asian (SAS)

AF:

0.00

AC:

AN:

21512

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4098

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1488

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

627120

Other (OTH)

AF:

0.00

AC:

AN:

23660

GnomAD4 genome

Cov.:

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

Pathogenic

0.81

BayesDel_addAF

Benign

-0.0015

BayesDel_noAF

Benign

-0.24

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.010

Eigen

Benign

-0.11

Eigen_PC

Benign

0.0086

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.67

M_CAP

Pathogenic

0.77

MetaRNN

Benign

0.23

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

PhyloP100

5.2

PrimateAI

Pathogenic

0.94

PROVEAN

Benign

-0.35

REVEL

Benign

0.090

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.23

Vest4

0.16

MutPred

0.30

Gain of ubiquitination at E3 (P = 0.0069)

MVP

0.65

MPC

1.1

ClinPred

0.70

GERP RS

4.0

PromoterAI

-0.54

Under-expression

(source)

Varity_R

0.66

gMVP

0.75

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over