Variant 7-140673700-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000072869.9(ADCK2):c.370C>T(p.Pro124Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000698 in 1,612,178 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00061 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00071 ( 0 hom. )

Consequence

ADCK2
ENST00000072869.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.485

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0064949095).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ADCK2	NM_052853.4 linkuse as main transcript	c.370C>T	p.Pro124Ser	missense_variant	1/8	ENST00000072869.9	NP_443085.2
ADCK2	XM_011516675.4 linkuse as main transcript	c.370C>T	p.Pro124Ser	missense_variant	1/7		XP_011514977.1
ADCK2	XM_006716170.5 linkuse as main transcript	c.370C>T	p.Pro124Ser	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.370C>T	p.Pro124Ser	missense_variant	1/8	1	NM_052853.4	ENSP00000072869	P1
ADCK2	ENST00000476491.5 linkuse as main transcript	c.370C>T	p.Pro124Ser	missense_variant	1/8	1		ENSP00000420512
DENND2A	ENST00000489552.1 linkuse as main transcript	c.-146+174G>A		intron_variant		4		ENSP00000418088

Frequencies

GnomAD3 genomes

AF:

0.000612

AC:

AN:

152048

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.0143

Gnomad AMR

AF:

0.0000655

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:

0.00107

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000364

AC:

AN:

250048

Hom.:

AF XY:

0.000385

AC XY:

AN XY:

135206

show subpopulations

Gnomad AFR exome

AF:

0.000123

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:

0.0000964

Gnomad NFE exome

AF:

0.000767

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000708

AC:

1033

AN:

1460012

Hom.:

Cov.:

AF XY:

0.000647

AC XY:

470

AN XY:

726352

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0000579

Gnomad4 NFE exome

AF:

0.000903

Gnomad4 OTH exome

AF:

0.000381

GnomAD4 genome

AF:

0.000611

AC:

AN:

152166

Hom.:

Cov.:

AF XY:

0.000591

AC XY:

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.000144

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00107

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000714

Hom.:

Bravo

AF:

0.000529

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.000338

AC:

EpiCase

AF:

0.000600

EpiControl

AF:

0.000593

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

Apr 09, 2024

The c.370C>T (p.P124S) alteration is located in exon 1 (coding exon 1) of the ADCK2 gene. This alteration results from a C to T substitution at nucleotide position 370, causing the proline (P) at amino acid position 124 to be replaced by a serine (S). 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

0.088

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0070

T;.

Eigen

Benign

-0.12

Eigen_PC

Benign

-0.079

FATHMM_MKL

Benign

0.34

LIST_S2

Benign

0.73

T;T

M_CAP

Benign

0.010

MetaRNN

Benign

0.0065

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.8

L;.

MutationTaster

Benign

0.96

D;D

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.9

N;N

REVEL

Benign

0.11

Sift

Benign

0.20

T;T

Sift4G

Benign

0.25

T;T

Polyphen

0.51

P;P

Vest4

0.083

MVP

0.62

MPC

0.76

ClinPred

0.13

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.22

gMVP

0.25

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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