rs758398844

Variant summary

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

The NM_138370.3(PKDCC):ā€‹c.17C>Gā€‹(p.Ala6Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000406 in 1,207,346 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: š‘“ 0.0000068 ( 0 hom., cov: 30)
Exomes š‘“: 0.000045 ( 0 hom. )

Consequence

PKDCC
NM_138370.3 missense

Scores

2
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.409
Variant links:
Genes affected
PKDCC (HGNC:25123): (protein kinase domain containing, cytoplasmic) Enables non-membrane spanning protein tyrosine kinase activity. Involved in peptidyl-tyrosine phosphorylation and skeletal system development. Located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

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=0.10490978).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PKDCCNM_138370.3 linkc.17C>G p.Ala6Gly missense_variant Exon 1 of 7 ENST00000294964.6 NP_612379.2 Q504Y2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PKDCCENST00000294964.6 linkc.17C>G p.Ala6Gly missense_variant Exon 1 of 7 1 NM_138370.3 ENSP00000294964.5 Q504Y2
PKDCCENST00000401498.6 linkn.17C>G non_coding_transcript_exon_variant Exon 1 of 8 5 ENSP00000385220.2 F8WB71

Frequencies

GnomAD3 genomes
AF:
0.00000683
AC:
1
AN:
146348
Hom.:
0
Cov.:
30
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:
0.0000152
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000452
AC:
48
AN:
1060998
Hom.:
0
Cov.:
31
AF XY:
0.0000485
AC XY:
25
AN XY:
515534
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:
0.000322
Gnomad4 NFE exome
AF:
0.0000423
Gnomad4 OTH exome
AF:
0.000102
GnomAD4 genome
AF:
0.00000683
AC:
1
AN:
146348
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
71192
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:
0.0000152
Gnomad4 OTH
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.17
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.44
CADD
Benign
20
DANN
Benign
0.94
DEOGEN2
Benign
0.046
T
Eigen
Benign
-0.43
Eigen_PC
Benign
-0.34
FATHMM_MKL
Benign
0.11
N
LIST_S2
Benign
0.43
T
M_CAP
Benign
0.030
D
MetaRNN
Benign
0.10
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.34
N
PrimateAI
Uncertain
0.78
T
PROVEAN
Benign
-0.69
N
REVEL
Benign
0.031
Sift
Benign
0.078
T
Sift4G
Uncertain
0.034
D
Polyphen
0.40
B
Vest4
0.13
MutPred
0.28
Loss of helix (P = 0.0041);
MVP
0.55
MPC
1.9
ClinPred
0.26
T
GERP RS
2.6
Varity_R
0.089
gMVP
0.38

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: rs758398844; hg19: chr2-42275356; API