chr2-42048475-G-C

Variant names:

• chr2-42048475-G-C
• rs1223783222
• NM_138370.3:c.276G>C

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_138370.3(PKDCC):​c.276G>C​(p.Pro92Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. P92P) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PKDCC NM_138370.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.190
• 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: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 2-42048475-G-C is Benign according to our data. Variant chr2-42048475-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 1988899.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.19 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKDCC	NM_138370.3	c.276G>C	p.Pro92Pro	synonymous_variant	Exon 1 of 7	ENST00000294964.6	NP_612379.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PKDCC	ENST00000294964.6	c.276G>C	p.Pro92Pro	synonymous_variant	Exon 1 of 7	1	NM_138370.3	ENSP00000294964.5
PKDCC	ENST00000401498.6	n.199-65G>C		intron_variant	Intron 1 of 7	5		ENSP00000385220.2
PKDCC	ENST00000485578.1	n.-104G>C		upstream_gene_variant		2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 899392 Hom.: 0 Cov.: 20 AF XY: 0.00 AC XY: 0 AN XY: 423900

African (AFR) AF: 0.00 AC: 0 AN: 17098

American (AMR) AF: 0.00 AC: 0 AN: 2904

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6940

East Asian (EAS) AF: 0.00 AC: 0 AN: 7710

South Asian (SAS) AF: 0.00 AC: 0 AN: 18028

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7538

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1960

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 806070

Other (OTH) AF: 0.00 AC: 0 AN: 31144

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 17, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	12
DANN	Benign	0.86
PhyloP100		0.19
PromoterAI		-0.021	Neutral
Mutation Taster		=100/0	polymorphism

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: rs1223783222; hg19: chr2-42275615;