Variant 7-140673740-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_052853.4(ADCK2):c.410C>T(p.Ala137Val) variant causes a missense change. The variant allele was found at a frequency of 0.00366 in 1,612,986 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0024 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0038 ( 19 hom. )

Consequence

ADCK2
NM_052853.4 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 5.28

Variant links:

Genes affected

ADCK2 (HGNC:19039): (aarF domain containing kinase 2) Predicted to enable ATP binding activity and protein serine/threonine kinase activity. Predicted to be involved in protein phosphorylation. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ADCK2 links:

DENND2A (HGNC:22212): (DENN domain containing 2A) Enables guanyl-nucleotide exchange factor activity. Involved in retrograde transport, endosome to Golgi. Located in actin cytoskeleton. [provided by Alliance of Genome Resources, Apr 2022]

DENND2A links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008479744).

BP6

Variant 7-140673740-C-T is Benign according to our data. Variant chr7-140673740-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3053008.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 19 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADCK2	NM_052853.4 link	c.410C>T	p.Ala137Val	missense_variant	1/8	ENST00000072869.9	NP_443085.2	Q7Z695A4D1T6
ADCK2	XM_011516675.4 link	c.410C>T	p.Ala137Val	missense_variant	1/7		XP_011514977.1
ADCK2	XM_006716170.5 link	c.410C>T	p.Ala137Val	missense_variant	1/7		XP_006716233.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ADCK2	ENST00000072869.9 link	c.410C>T	p.Ala137Val	missense_variant	1/8	1	NM_052853.4	ENSP00000072869.4	Q7Z695
ADCK2	ENST00000476491.5 link	c.410C>T	p.Ala137Val	missense_variant	1/8	1		ENSP00000420512.1	C9JE15
DENND2A	ENST00000489552.1 link	c.-146+134G>A		intron_variant		4		ENSP00000418088.1	C9JAA0

Frequencies

GnomAD3 genomes

AF:

0.00239

AC:

364

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000772

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00406

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00169

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00359

Gnomad OTH

AF:

0.00334

GnomAD3 exomes

AF:

0.00210

AC:

525

AN:

250482

Hom.:

AF XY:

0.00205

AC XY:

277

AN XY:

135418

show subpopulations

Gnomad AFR exome

AF:

0.000554

Gnomad AMR exome

AF:

0.00202

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000901

Gnomad NFE exome

AF:

0.00368

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.00379

AC:

5536

AN:

1460756

Hom.:

Cov.:

AF XY:

0.00371

AC XY:

2697

AN XY:

726718

show subpopulations

Gnomad4 AFR exome

AF:

0.000538

Gnomad4 AMR exome

AF:

0.00212

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00103

Gnomad4 NFE exome

AF:

0.00462

Gnomad4 OTH exome

AF:

0.00361

GnomAD4 genome

AF:

0.00239

AC:

364

AN:

152230

Hom.:

Cov.:

AF XY:

0.00216

AC XY:

161

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.000770

Gnomad4 AMR

AF:

0.00405

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00169

Gnomad4 NFE

AF:

0.00359

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00323

Hom.:

Bravo

AF:

0.00244

TwinsUK

AF:

0.00458

AC:

ALSPAC

AF:

0.00363

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00337

AC:

ExAC

AF:

0.00194

AC:

235

EpiCase

AF:

0.00463

EpiControl

AF:

0.00403

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ADCK2-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 20, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.017

T;.

Eigen

Uncertain

0.23

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Uncertain

0.78

LIST_S2

Uncertain

0.88

D;D

M_CAP

Benign

0.0092

MetaRNN

Benign

0.0085

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

M;.

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-2.2

N;N

REVEL

Benign

0.11

Sift

Benign

0.12

T;T

Sift4G

Benign

0.14

T;T

Polyphen

0.85

P;P

Vest4

0.19

MVP

0.31

MPC

0.84

ClinPred

0.029

GERP RS

4.6

Varity_R

0.25

gMVP

0.60

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over