Genetic Variant CDC73:c.729+46_729+51dupAGAGAG (chr1-193142098-T-TGAGAGA) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_024529.5(CDC73):c.729+46_729+51dupAGAGAG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CDC73
NM_024529.5 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.164

Variant links:

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 links:

ENSG00000308280 (HGNC:):

ENSG00000308280 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDC73	NM_024529.5 link	c.729+46_729+51dupAGAGAG		intron_variant	Intron 7 of 16	ENST00000367435.5	NP_078805.3	Q6P1J9
CDC73	XM_006711537.5 link	c.729+46_729+51dupAGAGAG		intron_variant	Intron 7 of 10		XP_006711600.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDC73	ENST00000367435.5 link	c.729+32_729+33insGAGAGA		intron_variant	Intron 7 of 16	1	NM_024529.5	ENSP00000356405.4		Q6P1J9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1289188

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

648192

African (AFR)

AF:

0.00

AC:

AN:

29700

American (AMR)

AF:

0.00

AC:

AN:

43708

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24712

East Asian (EAS)

AF:

0.00

AC:

AN:

37648

South Asian (SAS)

AF:

0.00

AC:

AN:

81530

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51670

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5420

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

960404

Other (OTH)

AF:

0.00

AC:

AN:

54396

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.16

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over