rs4952590

Variant names:

• chr2-42049781-C-T
• rs4952590
• NM_138370.3:c.639+943C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 19 publications found

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)

ACMG classification

Our verdict: Benign. The variant received -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKDCC	NM_138370.3	MANE Select	c.639+943C>T		intron	N/A	NP_612379.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKDCC	ENST00000294964.6	TSL:1 MANE Select	c.639+943C>T		intron	N/A	ENSP00000294964.5
	PKDCC	ENST00000401498.6	TSL:5	n.497+943C>T		intron	N/A	ENSP00000385220.2
	PKDCC	ENST00000485578.1	TSL:2	n.260+943C>T		intron	N/A

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

African (AFR) AF: 0.349 AC: 14476 AN: 41452

American (AMR) AF: 0.376 AC: 5736 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0847 AC: 294 AN: 3470

East Asian (EAS) AF: 0.419 AC: 2161 AN: 5152

South Asian (SAS) AF: 0.196 AC: 943 AN: 4808

European-Finnish (FIN) AF: 0.0606 AC: 643 AN: 10608

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.131 AC: 8872 AN: 67982

Other (OTH) AF: 0.215 AC: 454 AN: 2114

Alfa AF: 0.172 Hom.: 8297

Bravo AF: 0.258

Asia WGS AF: 0.309 AC: 1075 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.0
DANN	Benign	0.77
PhyloP100		-0.31
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4952590; hg19: chr2-42276921;