rs1044305

chr2-42057744-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.925

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
PKDCC	NM_138370.3	c.*56T>C		3_prime_UTR_variant	7/7	ENST00000294964.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PKDCC	ENST00000294964.6	c.*56T>C		3_prime_UTR_variant	7/7	1	NM_138370.3	P1

Frequencies

GnomAD3 genomes AF: 0.197 AC: 30019 AN: 152076 Hom.: 3827 Cov.: 33

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.: 20 AF XY: 0.159 AC XY: 107549 AN XY: 676040

Gnomad4 AFR exome AF: 0.271

Gnomad4 AMR exome AF: 0.490

Gnomad4 ASJ exome AF: 0.0797

Gnomad4 EAS exome AF: 0.457

Gnomad4 SAS exome AF: 0.195

Gnomad4 FIN exome AF: 0.0790

Gnomad4 NFE exome AF: 0.136

Gnomad4 OTH exome AF: 0.164

GnomAD4 genome AF: 0.198 AC: 30091 AN: 152194 Hom.: 3843 Cov.: 33 AF XY: 0.199 AC XY: 14801 AN XY: 74410

Gnomad4 AFR AF: 0.265

Gnomad4 AMR AF: 0.353

Gnomad4 ASJ AF: 0.0772

Gnomad4 EAS AF: 0.449

Gnomad4 SAS AF: 0.205

Gnomad4 FIN AF: 0.0718

Gnomad4 NFE AF: 0.131

Gnomad4 OTH AF: 0.191

Alfa AF: 0.149 Hom.: 2179

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
Dann	Benign	0.72

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

Other links and lift over

dbSNP: rs1044305; hg19: chr2-42284884; COSMIC: COSV54308676; COSMIC: COSV54308676;