Genetic Variant PKDCC:p.Tyr70Ser (chr2-42048408-A-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_138370.3(PKDCC):c.209A>C(p.Tyr70Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y70C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PKDCC
NM_138370.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.649

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

rhizomelic limb shortening with dysmorphic features
Inheritance: AR Classification: STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

PKDCC links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2601205).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138370.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKDCC	NM_138370.3	MANE Select	c.209A>C	p.Tyr70Ser	missense	Exon 1 of 7	NP_612379.2	Q504Y2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PKDCC	ENST00000294964.6	TSL:1 MANE Select	c.209A>C	p.Tyr70Ser	missense	Exon 1 of 7	ENSP00000294964.5	Q504Y2
PKDCC	ENST00000914294.1		c.209A>C	p.Tyr70Ser	missense	Exon 1 of 7	ENSP00000584353.1
PKDCC	ENST00000953637.1		c.209A>C	p.Tyr70Ser	missense	Exon 1 of 7	ENSP00000623696.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

994258

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

474904

African (AFR)

AF:

0.00

AC:

AN:

19006

American (AMR)

AF:

0.00

AC:

AN:

5928

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

9702

East Asian (EAS)

AF:

0.00

AC:

AN:

17354

South Asian (SAS)

AF:

0.00

AC:

AN:

22158

European-Finnish (FIN)

AF:

0.00

AC:

AN:

14760

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2348

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

866864

Other (OTH)

AF:

0.00

AC:

AN:

36138

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.73

BayesDel_addAF

Benign

-0.021

BayesDel_noAF

Benign

-0.27

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.12

Eigen

Benign

0.093

Eigen_PC

Benign

0.019

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.49

M_CAP

Benign

0.015

MetaRNN

Benign

0.26

MetaSVM

Benign

-0.82

MutationAssessor

Benign

0.69

PhyloP100

0.65

PrimateAI

Pathogenic

0.94

PROVEAN

Benign

-1.3

REVEL

Uncertain

0.33

Sift

Benign

0.035

Sift4G

Benign

0.15

Polyphen

0.99

Vest4

0.20

MutPred

0.14

Loss of stability (P = 0.0835)

MVP

0.82

MPC

2.6

ClinPred

0.48

GERP RS

2.2

PromoterAI

0.0051

Neutral

(source)

Varity_R

0.22

gMVP

0.54

Mutation Taster

=53/47

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over