rs4952590

Positions:

• chr2-42049781-C-T

Variant summary

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

The NM_138370.3(PKDCC):​c.639+943C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 152,064 control chromosomes in the GnomAD database, including 4,979 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 0.22 (4979 hom., cov: 31)
• Consequence: PKDCC NM_138370.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.311

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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.405 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PKDCC	NM_138370.3	c.639+943C>T		intron_variant		ENST00000294964.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PKDCC	ENST00000294964.6	c.639+943C>T		intron_variant		1	NM_138370.3	P1
PKDCC	ENST00000401498.6	c.497+943C>T		intron_variant, NMD_transcript_variant		5
PKDCC	ENST00000485578.1	n.260+943C>T		intron_variant, non_coding_transcript_variant		2
PKDCC	ENST00000492861.1	n.65+943C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33582 AN: 151946 Hom.: 4951 Cov.: 31

Gnomad AFR AF: 0.349

Gnomad AMI AF: 0.0768

Gnomad AMR AF: 0.375

Gnomad ASJ AF: 0.0847

Gnomad EAS AF: 0.419

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.0606

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.209

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.221 AC: 33674 AN: 152064 Hom.: 4979 Cov.: 31 AF XY: 0.221 AC XY: 16464 AN XY: 74330

Gnomad4 AFR AF: 0.349

Gnomad4 AMR AF: 0.376

Gnomad4 ASJ AF: 0.0847

Gnomad4 EAS AF: 0.419

Gnomad4 SAS AF: 0.196

Gnomad4 FIN AF: 0.0606

Gnomad4 NFE AF: 0.131

Gnomad4 OTH AF: 0.215

Alfa AF: 0.145 Hom.: 3392

Bravo AF: 0.258

Asia WGS AF: 0.309 AC: 1075 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.0
DANN	Benign	0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs4952590; hg19: chr2-42276921;