7-140674142-C-T

Variant names:

Variant summary

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

The NM_052853.4(ADCK2):c.812C>T(p.Ser271Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,613,936 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 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

ADCK2
NM_052853.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.938

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=0.08147475).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADCK2	NM_052853.4 link	c.812C>T	p.Ser271Leu	missense_variant	Exon 1 of 8	ENST00000072869.9	NP_443085.2	Q7Z695A4D1T6
ADCK2	XM_011516675.4 link	c.812C>T	p.Ser271Leu	missense_variant	Exon 1 of 7		XP_011514977.1
ADCK2	XM_006716170.5 link	c.812C>T	p.Ser271Leu	missense_variant	Exon 1 of 7		XP_006716233.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ADCK2	ENST00000072869.9 link	c.812C>T	p.Ser271Leu	missense_variant	Exon 1 of 8	1	NM_052853.4	ENSP00000072869.4	Q7Z695
ADCK2	ENST00000476491.5 link	c.812C>T	p.Ser271Leu	missense_variant	Exon 1 of 8	1		ENSP00000420512.1	C9JE15
ADCK2	ENST00000483369.5 link	c.323C>T	p.Ser108Leu	missense_variant	Exon 1 of 8	5		ENSP00000417367.1	H7C4I2
DENND2A	ENST00000489552.1 link	c.-414G>A		upstream_gene_variant		4		ENSP00000418088.1	C9JAA0

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152100

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251144

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135854

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:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461836

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727218

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152100

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74298

show subpopulations

Gnomad4 AFR

AF:

0.0000242

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 20, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.812C>T (p.S271L) 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 812, causing the serine (S) at amino acid position 271 to be replaced by a leucine (L). 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

0.094

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0038

T;.

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.048

LIST_S2

Uncertain

0.88

D;D

M_CAP

Benign

0.0042

MetaRNN

Benign

0.081

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.4

L;.

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.6

N;N

REVEL

Benign

0.066

Sift

Benign

0.10

T;T

Sift4G

Benign

0.20

T;T

Polyphen

0.49

P;P

Vest4

0.13

MutPred

0.50

Loss of disorder (P = 0.0432);Loss of disorder (P = 0.0432);

MVP

0.21

MPC

0.43

ClinPred

0.14

GERP RS

1.4

Varity_R

0.041

gMVP

0.36

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