dbSNP rs1044305: PKDCC:c.*56T>C (chr2-42057744-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_138370.3(PKDCC):c.*56T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 1,505,726 control chromosomes in the GnomAD database, including 26,600 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.20 ( 3843 hom., cov: 33)

Exomes 𝑓: 0.16 ( 22757 hom. )

Consequence

PKDCC
NM_138370.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.925

Publications

7 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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.433 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKDCC	NM_138370.3 link	c.*56T>C		3_prime_UTR_variant	Exon 7 of 7	ENST00000294964.6	NP_612379.2	Q504Y2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PKDCC	ENST00000294964.6 link	c.*56T>C		3_prime_UTR_variant	Exon 7 of 7	1	NM_138370.3	ENSP00000294964.5		Q504Y2

Frequencies

GnomAD3 genomes

AF:

0.197

AC:

30019

AN:

152076

Hom.:

3827

Cov.:

show subpopulations

Gnomad AFR

AF:

0.265

Gnomad AMI

AF:

0.0625

Gnomad AMR

AF:

0.352

Gnomad ASJ

AF:

0.0772

Gnomad EAS

AF:

0.448

Gnomad SAS

AF:

0.204

Gnomad FIN

AF:

0.0718

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.130

Gnomad OTH

AF:

0.188

GnomAD4 exome

AF:

0.161

AC:

217431

AN:

1353532

Hom.:

22757

Cov.:

AF XY:

0.159

AC XY:

107549

AN XY:

676040

show subpopulations

African (AFR)

AF:

0.271

AC:

8424

AN:

31096

American (AMR)

AF:

0.490

AC:

20617

AN:

42104

Ashkenazi Jewish (ASJ)

AF:

0.0797

AC:

1997

AN:

25062

East Asian (EAS)

AF:

0.457

AC:

17508

AN:

38296

South Asian (SAS)

AF:

0.195

AC:

15920

AN:

81804

European-Finnish (FIN)

AF:

0.0790

AC:

3997

AN:

50566

Middle Eastern (MID)

AF:

0.0904

AC:

435

AN:

4812

European-Non Finnish (NFE)

AF:

0.136

AC:

139229

AN:

1023220

Other (OTH)

AF:

0.164

AC:

9304

AN:

56572

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

8448

16895

25343

33790

42238

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5368

10736

16104

21472

26840

<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

AF:

0.198

AC:

30091

AN:

152194

Hom.:

3843

Cov.:

AF XY:

0.199

AC XY:

14801

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.265

AC:

11008

AN:

41534

American (AMR)

AF:

0.353

AC:

5396

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0772

AC:

268

AN:

3472

East Asian (EAS)

AF:

0.449

AC:

2307

AN:

5142

South Asian (SAS)

AF:

0.205

AC:

989

AN:

4822

European-Finnish (FIN)

AF:

0.0718

AC:

762

AN:

10612

Middle Eastern (MID)

AF:

0.0918

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.131

AC:

8874

AN:

68000

Other (OTH)

AF:

0.191

AC:

403

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1200

2400

3599

4799

5999

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

314

628

942

1256

1570

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.159

Hom.:

3565

Bravo

AF:

0.228

Asia WGS

AF:

0.307

AC:

1067

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

6.6

(source)

DANN

Benign

0.72

PhyloP100

-0.93

Mutation Taster

=100/0

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over