chr7-140694739-C-T

Variant summary

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

The NM_052853.4(ADCK2):​c.1817C>T​(p.Pro606Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000297 in 1,613,992 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

ADCK2
NM_052853.4 missense

Scores

8
8
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.57
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.1817C>T p.Pro606Leu missense_variant Exon 8 of 8 ENST00000072869.9 NP_443085.2 Q7Z695A4D1T6
ADCK2XM_011516675.4 linkc.1721C>T p.Pro574Leu missense_variant Exon 7 of 7 XP_011514977.1
ADCK2XM_006716170.5 linkc.1565C>T p.Pro522Leu missense_variant Exon 7 of 7 XP_006716233.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ADCK2ENST00000072869.9 linkc.1817C>T p.Pro606Leu missense_variant Exon 8 of 8 1 NM_052853.4 ENSP00000072869.4 Q7Z695

Frequencies

GnomAD3 genomes
AF:
0.0000526
AC:
8
AN:
152190
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00173
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000676
AC:
17
AN:
251318
Hom.:
0
AF XY:
0.0000515
AC XY:
7
AN XY:
135844
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00139
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:
0.000163
GnomAD4 exome
AF:
0.0000274
AC:
40
AN:
1461802
Hom.:
0
Cov.:
30
AF XY:
0.0000248
AC XY:
18
AN XY:
727198
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00119
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.000116
GnomAD4 genome
AF:
0.0000526
AC:
8
AN:
152190
Hom.:
0
Cov.:
32
AF XY:
0.0000672
AC XY:
5
AN XY:
74358
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00173
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000675
Hom.:
0
Bravo
AF:
0.0000340
ExAC
AF:
0.0000412
AC:
5
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 24, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1817C>T (p.P606L) alteration is located in exon 8 (coding exon 8) of the ADCK2 gene. This alteration results from a C to T substitution at nucleotide position 1817, causing the proline (P) at amino acid position 606 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
Pathogenic
0.72
BayesDel_addAF
Uncertain
0.15
D
BayesDel_noAF
Uncertain
-0.030
CADD
Pathogenic
29
DANN
Uncertain
1.0
DEOGEN2
Benign
0.40
T;.
Eigen
Pathogenic
0.81
Eigen_PC
Pathogenic
0.70
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.93
D;D
M_CAP
Uncertain
0.16
D
MetaRNN
Uncertain
0.65
D;D
MetaSVM
Benign
-0.31
T
MutationAssessor
Pathogenic
3.6
H;.
PrimateAI
Uncertain
0.72
T
PROVEAN
Pathogenic
-9.6
D;D
REVEL
Uncertain
0.56
Sift
Pathogenic
0.0
D;D
Sift4G
Pathogenic
0.0
D;D
Polyphen
1.0
D;.
Vest4
0.84
MutPred
0.59
Loss of disorder (P = 0.0514);.;
MVP
0.54
MPC
1.4
ClinPred
1.0
D
GERP RS
4.1
Varity_R
0.86
gMVP
0.77

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: rs772181288; hg19: chr7-140394539; API