Variant 7-140673454-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_052853.4(ADCK2):c.124C>T(p.Leu42Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00535 in 1,608,808 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0034 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0055 ( 31 hom. )

Consequence

ADCK2
NM_052853.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0240

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0056689084).

BP6

Variant 7-140673454-C-T is Benign according to our data. Variant chr7-140673454-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2658020.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADCK2	NM_052853.4 linkuse as main transcript	c.124C>T	p.Leu42Phe	missense_variant	1/8	ENST00000072869.9	NP_443085.2	Q7Z695A4D1T6
ADCK2	XM_011516675.4 linkuse as main transcript	c.124C>T	p.Leu42Phe	missense_variant	1/7		XP_011514977.1
ADCK2	XM_006716170.5 linkuse as main transcript	c.124C>T	p.Leu42Phe	missense_variant	1/7		XP_006716233.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ADCK2	ENST00000072869.9 linkuse as main transcript	c.124C>T	p.Leu42Phe	missense_variant	1/8	1	NM_052853.4	ENSP00000072869.4	Q7Z695
ADCK2	ENST00000476491.5 linkuse as main transcript	c.124C>T	p.Leu42Phe	missense_variant	1/8	1		ENSP00000420512.1	C9JE15
DENND2A	ENST00000489552.1 linkuse as main transcript	c.-146+420G>A		intron_variant		4		ENSP00000418088.1	C9JAA0

Frequencies

GnomAD3 genomes

AF:

0.00345

AC:

525

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00150

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00124

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.00198

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00579

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00393

AC:

932

AN:

237314

Hom.:

AF XY:

0.00399

AC XY:

519

AN XY:

130236

show subpopulations

Gnomad AFR exome

AF:

0.00137

Gnomad AMR exome

AF:

0.00280

Gnomad ASJ exome

AF:

0.00185

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00268

Gnomad FIN exome

AF:

0.00228

Gnomad NFE exome

AF:

0.00608

Gnomad OTH exome

AF:

0.00564

GnomAD4 exome

AF:

0.00555

AC:

8078

AN:

1456508

Hom.:

Cov.:

AF XY:

0.00554

AC XY:

4014

AN XY:

724172

show subpopulations

Gnomad4 AFR exome

AF:

0.00108

Gnomad4 AMR exome

AF:

0.00262

Gnomad4 ASJ exome

AF:

0.00154

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.00265

Gnomad4 FIN exome

AF:

0.00161

Gnomad4 NFE exome

AF:

0.00653

Gnomad4 OTH exome

AF:

0.00516

GnomAD4 genome

AF:

0.00344

AC:

524

AN:

152300

Hom.:

Cov.:

AF XY:

0.00306

AC XY:

228

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.00149

Gnomad4 AMR

AF:

0.00124

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00207

Gnomad4 FIN

AF:

0.00198

Gnomad4 NFE

AF:

0.00579

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00521

Hom.:

Bravo

AF:

0.00345

TwinsUK

AF:

0.00297

AC:

ALSPAC

AF:

0.00571

AC:

ESP6500AA

AF:

0.00114

AC:

ESP6500EA

AF:

0.00642

AC:

ExAC

AF:

0.00431

AC:

521

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2022

ADCK2: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.0033

T;.

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.52

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.65

T;T

M_CAP

Benign

0.0083

MetaRNN

Benign

0.0057

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

L;.

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.74

N;N

REVEL

Benign

0.014

Sift

Benign

0.20

T;T

Sift4G

Benign

0.17

T;T

Polyphen

0.053

B;B

Vest4

0.15

MVP

0.35

MPC

0.55

ClinPred

0.0041

GERP RS

2.7

Varity_R

0.070

gMVP

0.24

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