chr2-42048430-C-G

Variant names:

• chr2-42048430-C-G
• rs1230128150
• NM_138370.3:c.231C>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_138370.3(PKDCC):​c.231C>G​(p.Pro77Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000104 in 963,400 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P77P) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000010 (0 hom.)
• Consequence: PKDCC NM_138370.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.196
• Publications: 0 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: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP7: Synonymous conserved (PhyloP=-0.196 with no splicing effect.

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.231C>G	p.Pro77Pro	synonymous	Exon 1 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.231C>G	p.Pro77Pro	synonymous	Exon 1 of 7	ENSP00000294964.5	Q504Y2
	PKDCC	ENST00000914294.1		c.231C>G	p.Pro77Pro	synonymous	Exon 1 of 7	ENSP00000584353.1
	PKDCC	ENST00000953637.1		c.231C>G	p.Pro77Pro	synonymous	Exon 1 of 7	ENSP00000623696.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000104 AC: 1 AN: 963400 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 459248

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 18196

American (AMR) AF: 0.00 AC: 0 AN: 4868

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8568

East Asian (EAS) AF: 0.00 AC: 0 AN: 14316

South Asian (SAS) AF: 0.00 AC: 0 AN: 21216

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 11956

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2200

European-Non Finnish (NFE) AF: 0.00000118 AC: 1 AN: 847868

Other (OTH) AF: 0.00 AC: 0 AN: 34212

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	9.8
DANN	Benign	0.76
PhyloP100		-0.20
PromoterAI		-0.053	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1230128150; hg19: chr2-42275570;