Variant chr2-42048246-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_138370.3(PKDCC):c.47T>G(p.Phe16Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000243 in 1,275,210 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000048 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

PKDCC
NM_138370.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.706

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]

PKDCC links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.29766074).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PKDCC	NM_138370.3 linkuse as main transcript	c.47T>G	p.Phe16Cys	missense_variant	1/7	ENST00000294964.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PKDCC	ENST00000294964.6 linkuse as main transcript	c.47T>G	p.Phe16Cys	missense_variant	1/7	1	NM_138370.3	P1
PKDCC	ENST00000401498.6 linkuse as main transcript	c.47T>G	p.Phe16Cys	missense_variant, NMD_transcript_variant	1/8	5

Frequencies

GnomAD3 genomes

AF:

0.0000478

AC:

AN:

146554

Hom.:

Cov.:

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:

0.000106

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000213

AC:

AN:

1128656

Hom.:

Cov.:

AF XY:

0.0000163

AC XY:

AN XY:

552934

show subpopulations

Gnomad4 AFR exome

AF:

0.0000450

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:

0.0000214

Gnomad4 OTH exome

AF:

0.0000469

GnomAD4 genome

AF:

0.0000478

AC:

AN:

146554

Hom.:

Cov.:

AF XY:

0.0000280

AC XY:

AN XY:

71306

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:

0.000106

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 21, 2022

The c.47T>G (p.F16C) alteration is located in exon 1 (coding exon 1) of the PKDCC gene. This alteration results from a T to G substitution at nucleotide position 47, causing the phenylalanine (F) at amino acid position 16 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

Uncertain

0.44

BayesDel_addAF

Benign

-0.021

BayesDel_noAF

Benign

-0.27

CADD

Uncertain

DANN

Benign

0.96

DEOGEN2

Benign

0.12

Eigen

Benign

0.060

Eigen_PC

Benign

0.016

FATHMM_MKL

Benign

0.43

LIST_S2

Benign

0.51

M_CAP

Uncertain

0.086

MetaRNN

Benign

0.30

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.55

MutationTaster

Benign

0.98

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

-0.61

REVEL

Benign

0.17

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.99

Vest4

0.38

MutPred

0.38

Gain of catalytic residue at L17 (P = 0.0143);

MVP

0.66

MPC

2.5

ClinPred

0.43

GERP RS

1.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

Varity_R

0.23

gMVP

0.28

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