rs1044305

Variant names:

• chr2-42057744-T-C
• rs1044305
• NM_138370.3:c.*56T>C

Variant summary

Our verdict is Benign. The variant received -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
• 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 -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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKDCC	NM_138370.3	MANE Select	c.*56T>C		3_prime_UTR	Exon 7 of 7	NP_612379.2	Q504Y2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKDCC	ENST00000294964.6	TSL:1 MANE Select	c.*56T>C		3_prime_UTR	Exon 7 of 7	ENSP00000294964.5	Q504Y2
	PKDCC	ENST00000914294.1		c.*56T>C		3_prime_UTR	Exon 7 of 7	ENSP00000584353.1
	PKDCC	ENST00000953637.1		c.*56T>C		3_prime_UTR	Exon 7 of 7	ENSP00000623696.1

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

African (AFR) AF: 0.271 AC: 8424 AN: 31096

American (AMR) AF: 0.490 AC: 20617 AN: 42104

Ashkenazi Jewish (ASJ) AF: 0.0797 AC: 1997 AN: 25062

East Asian (EAS) AF: 0.457 AC: 17508 AN: 38296

South Asian (SAS) AF: 0.195 AC: 15920 AN: 81804

European-Finnish (FIN) AF: 0.0790 AC: 3997 AN: 50566

Middle Eastern (MID) AF: 0.0904 AC: 435 AN: 4812

European-Non Finnish (NFE) AF: 0.136 AC: 139229 AN: 1023220

Other (OTH) AF: 0.164 AC: 9304 AN: 56572

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

African (AFR) AF: 0.265 AC: 11008 AN: 41534

American (AMR) AF: 0.353 AC: 5396 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0772 AC: 268 AN: 3472

East Asian (EAS) AF: 0.449 AC: 2307 AN: 5142

South Asian (SAS) AF: 0.205 AC: 989 AN: 4822

European-Finnish (FIN) AF: 0.0718 AC: 762 AN: 10612

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.131 AC: 8874 AN: 68000

Other (OTH) AF: 0.191 AC: 403 AN: 2112

Alfa AF: 0.159 Hom.: 3565

Bravo AF: 0.228

Asia WGS AF: 0.307 AC: 1067 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.6
DANN	Benign	0.72
PhyloP100		-0.93
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: rs1044305; hg19: chr2-42284884; COSMIC: COSV54308676; COSMIC: COSV54308676;