Genetic Variant NM_138370.3:c.131C>A (chr2-42048330-C-A) – 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.131C>A(p.Ala44Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000193 in 1,037,546 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. A44A) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.0000019 ( 0 hom. )

Consequence

PKDCC
NM_138370.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.119

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:

Genome browser will be placed here

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=0.083597034).

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.131C>A	p.Ala44Asp	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.131C>A	p.Ala44Asp	missense	Exon 1 of 7	ENSP00000294964.5	Q504Y2
PKDCC	ENST00000914294.1		c.131C>A	p.Ala44Asp	missense	Exon 1 of 7	ENSP00000584353.1
PKDCC	ENST00000953637.1		c.131C>A	p.Ala44Asp	missense	Exon 1 of 7	ENSP00000623696.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000193

AC:

AN:

1037546

Hom.:

Cov.:

AF XY:

0.00000202

AC XY:

AN XY:

494704

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

20424

American (AMR)

AF:

0.00

AC:

AN:

6348

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

11602

East Asian (EAS)

AF:

0.00

AC:

AN:

22072

South Asian (SAS)

AF:

0.0000402

AC:

AN:

24890

European-Finnish (FIN)

AF:

0.00

AC:

AN:

18876

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2634

European-Non Finnish (NFE)

AF:

0.00000112

AC:

AN:

891382

Other (OTH)

AF:

0.00

AC:

AN:

39318

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.600

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.047

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.045

LIST_S2

Benign

0.38

M_CAP

Benign

0.054

MetaRNN

Benign

0.084

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

PhyloP100

-0.12

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-0.44

REVEL

Benign

0.085

Sift

Benign

0.047

Sift4G

Uncertain

0.058

Polyphen

0.0

Vest4

0.13

MutPred

0.19

Loss of MoRF binding (P = 0.0695)

MVP

0.46

MPC

2.5

ClinPred

0.19

GERP RS

2.1

PromoterAI

-0.0032

Neutral

(source)

Varity_R

0.19

gMVP

0.36

Mutation Taster

=68/32

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over