Variant chr7-140673640-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000072869.9(ADCK2):c.310G>T(p.Gly104Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000745 in 1,609,806 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

ADCK2
ENST00000072869.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.85

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10915348).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ADCK2	NM_052853.4 linkuse as main transcript	c.310G>T	p.Gly104Cys	missense_variant	1/8	ENST00000072869.9	NP_443085.2
ADCK2	XM_011516675.4 linkuse as main transcript	c.310G>T	p.Gly104Cys	missense_variant	1/7		XP_011514977.1
ADCK2	XM_006716170.5 linkuse as main transcript	c.310G>T	p.Gly104Cys	missense_variant	1/7		XP_006716233.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ADCK2	ENST00000072869.9 linkuse as main transcript	c.310G>T	p.Gly104Cys	missense_variant	1/8	1	NM_052853.4	ENSP00000072869	P1
ADCK2	ENST00000476491.5 linkuse as main transcript	c.310G>T	p.Gly104Cys	missense_variant	1/8	1		ENSP00000420512
DENND2A	ENST00000489552.1 linkuse as main transcript	c.-146+234C>A		intron_variant		4		ENSP00000418088

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

151906

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000162

AC:

AN:

247232

Hom.:

AF XY:

0.00000746

AC XY:

AN XY:

134092

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000519

Gnomad NFE exome

AF:

0.0000268

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000617

AC:

AN:

1457900

Hom.:

Cov.:

AF XY:

0.00000414

AC XY:

AN XY:

725442

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000605

Gnomad4 NFE exome

AF:

0.00000540

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

151906

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74168

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 26, 2023

The c.310G>T (p.G104C) alteration is located in exon 1 (coding exon 1) of the ADCK2 gene. This alteration results from a G to T substitution at nucleotide position 310, causing the glycine (G) at amino acid position 104 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.77

DEOGEN2

Benign

0.0026

T;.

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.46

LIST_S2

Benign

0.71

T;T

M_CAP

Benign

0.017

MetaRNN

Benign

0.11

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.1

L;.

MutationTaster

Benign

0.77

N;N

PrimateAI

Benign

0.48

PROVEAN

Benign

1.0

N;N

REVEL

Benign

0.093

Sift

Benign

0.075

T;T

Sift4G

Benign

0.18

T;T

Polyphen

0.0060

B;B

Vest4

0.14

MVP

0.49

MPC

0.54

ClinPred

0.071

GERP RS

2.5

Varity_R

0.14

gMVP

0.66

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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