rs2424

Variant names:

• chr2-42058435-T-A
• rs2424
• NM_138370.3:c.*747T>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 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 -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.

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.*747T>A		3_prime_UTR	Exon 7 of 7	NP_612379.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKDCC	ENST00000294964.6	TSL:1 MANE Select	c.*747T>A		3_prime_UTR	Exon 7 of 7	ENSP00000294964.5
	PKDCC	ENST00000490302.1	TSL:2	n.1413T>A		non_coding_transcript_exon	Exon 3 of 3
	PKDCC	ENST00000480099.1	TSL:5	n.*249T>A		downstream_gene	N/A

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.310 AC: 116 AN: 374

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AF: 0.750 AC: 3 AN: 4

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

African (AFR) AF: 0.130 AC: 5395 AN: 41510

American (AMR) AF: 0.142 AC: 2178 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.293 AC: 1018 AN: 3470

East Asian (EAS) AF: 0.000770 AC: 4 AN: 5192

South Asian (SAS) AF: 0.135 AC: 653 AN: 4826

European-Finnish (FIN) AF: 0.271 AC: 2860 AN: 10570

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.210 AC: 14270 AN: 67996

Other (OTH) AF: 0.182 AC: 385 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	16
DANN	Benign	0.91
PhyloP100		2.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2424; hg19: chr2-42285575;