1-193122197-G-GA

Position:

• chr1-193122197-G-GA

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_024529.5(CDC73):​c.-2dupA variant causes a start retained change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CDC73 NM_024529.5 start_retained
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.75

Genes affected

CDC73 (HGNC:16783): (cell division cycle 73) This gene encodes a tumor suppressor that is involved in transcriptional and post-transcriptional control pathways. The protein is a component of the the PAF protein complex, which associates with the RNA polymerase II subunit POLR2A and with a histone methyltransferase complex. This protein appears to facilitate the association of 3' mRNA processing factors with actively-transcribed chromatin. Mutations in this gene have been linked to hyperparathyroidism-jaw tumor syndrome, familial isolated hyperparathyroidism, and parathyroid carcinoma. [provided by RefSeq, Jul 2009]

CDC73 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDC73	NM_024529.5	c.-2dupA		start_retained_variant	1/17	ENST00000367435.5	NP_078805.3
CDC73	NM_024529.5	c.-2dupA		5_prime_UTR_variant	1/17	ENST00000367435.5	NP_078805.3
CDC73	XM_006711537.5	c.-2dupA		start_retained_variant	1/11		XP_006711600.1
CDC73	XM_006711537.5	c.-2dupA		5_prime_UTR_variant	1/11		XP_006711600.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDC73	ENST00000367435	c.-2dupA		start_retained_variant	1/17	1	NM_024529.5	ENSP00000356405.4
CDC73	ENST00000367435	c.-2dupA		5_prime_UTR_variant	1/17	1	NM_024529.5	ENSP00000356405.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Hereditary cancer-predisposing syndrome Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 24, 2022

The c.-2dupA variant is located in the 5 prime untranslated region (5'UTR) of the CDC73 gene. This variant results from an duplication of two nucleotides at nucleotide position -2 upstream from the first translated codon. This nucleotide position is highly conserved in available vertebrate species. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-193091327;