rs2424

Positions:

• chr2-42058435-T-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_138370.3(PKDCC):​c.*747T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 152,554 control chromosomes in the GnomAD database, including 2,744 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 0.18 (2728 hom., cov: 32)
  • Exomes 𝑓: 0.31 (16 hom.)
• Consequence: PKDCC NM_138370.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.93

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PKDCC	NM_138370.3	c.*747T>A		3_prime_UTR_variant	7/7	ENST00000294964.6	NP_612379.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PKDCC	ENST00000294964.6	c.*747T>A		3_prime_UTR_variant	7/7	1	NM_138370.3	ENSP00000294964.5
PKDCC	ENST00000490302.1	n.1413T>A		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27251 AN: 152056 Hom.: 2729 Cov.: 32

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.449

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.000769

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.271

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.184

GnomAD4 exome AF: 0.313 AC: 119 AN: 380 Hom.: 16 Cov.: 0 AF XY: 0.303 AC XY: 72 AN XY: 238

Gnomad4 FIN exome AF: 0.310

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.750

GnomAD4 genome AF: 0.179 AC: 27247 AN: 152174 Hom.: 2728 Cov.: 32 AF XY: 0.180 AC XY: 13397 AN XY: 74392

Gnomad4 AFR AF: 0.130

Gnomad4 AMR AF: 0.142

Gnomad4 ASJ AF: 0.293

Gnomad4 EAS AF: 0.000770

Gnomad4 SAS AF: 0.135

Gnomad4 FIN AF: 0.271

Gnomad4 NFE AF: 0.210

Gnomad4 OTH AF: 0.182

Alfa AF: 0.195 Hom.: 386

Bravo AF: 0.167

Asia WGS AF: 0.0690 AC: 242 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	16
DANN	Benign	0.91
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs2424; hg19: chr2-42285575;