7-140690782-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_052853.4(ADCK2):​c.1709C>G​(p.Ser570Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000547 in 1,461,804 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 30)
Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

ADCK2
NM_052853.4 missense

Scores

1
12
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.33
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]
NDUFB2 (HGNC:7697): (NADH:ubiquinone oxidoreductase subunit B2) The protein encoded by this gene is a subunit of the multisubunit NADH:ubiquinone oxidoreductase (complex I). Mammalian complex I is composed of 45 different subunits. This protein has NADH dehydrogenase activity and oxidoreductase activity. It plays a important role in transfering electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone. Hydropathy analysis revealed that this subunit and 4 other subunits have an overall hydrophilic pattern, even though they are found within the hydrophobic protein (HP) fraction of complex I. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ADCK2NM_052853.4 linkc.1709C>G p.Ser570Cys missense_variant Exon 7 of 8 ENST00000072869.9 NP_443085.2 Q7Z695A4D1T6
ADCK2XM_011516675.4 linkc.1613C>G p.Ser538Cys missense_variant Exon 6 of 7 XP_011514977.1
ADCK2XM_006716170.5 linkc.1457C>G p.Ser486Cys missense_variant Exon 6 of 7 XP_006716233.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ADCK2ENST00000072869.9 linkc.1709C>G p.Ser570Cys missense_variant Exon 7 of 8 1 NM_052853.4 ENSP00000072869.4 Q7Z695

Frequencies

GnomAD3 genomes
Cov.:
30
GnomAD3 exomes
AF:
0.00000795
AC:
2
AN:
251426
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135890
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:
0.00
Gnomad NFE exome
AF:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000547
AC:
8
AN:
1461804
Hom.:
0
Cov.:
31
AF XY:
0.00000275
AC XY:
2
AN XY:
727202
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:
0.00
Gnomad4 NFE exome
AF:
0.00000719
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
30
Alfa
AF:
0.000116
Hom.:
0
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 21, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1709C>G (p.S570C) alteration is located in exon 7 (coding exon 7) of the ADCK2 gene. This alteration results from a C to G substitution at nucleotide position 1709, causing the serine (S) at amino acid position 570 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
0.23
BayesDel_addAF
Uncertain
0.080
D
BayesDel_noAF
Benign
-0.11
CADD
Pathogenic
28
DANN
Uncertain
0.99
DEOGEN2
Benign
0.19
T;.;.
Eigen
Uncertain
0.61
Eigen_PC
Uncertain
0.53
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.88
D;D;D
M_CAP
Benign
0.045
D
MetaRNN
Uncertain
0.56
D;D;D
MetaSVM
Benign
-0.71
T
MutationAssessor
Uncertain
2.6
M;.;.
PrimateAI
Uncertain
0.53
T
PROVEAN
Uncertain
-3.4
D;D;D
REVEL
Uncertain
0.34
Sift
Uncertain
0.0020
D;D;D
Sift4G
Uncertain
0.0030
D;D;D
Polyphen
1.0
D;D;.
Vest4
0.54
MutPred
0.53
Loss of disorder (P = 0.0639);Loss of disorder (P = 0.0639);.;
MVP
0.52
MPC
1.4
ClinPred
0.95
D
GERP RS
4.4
Varity_R
0.43
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.

Other links and lift over

dbSNP: rs759406238; hg19: chr7-140390582; API