Variant NM_024529.5:c.1418-17C>G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_024529.5(CDC73):c.1418-17C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0769 in 1,592,552 control chromosomes in the GnomAD database, including 5,388 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.059 ( 364 hom., cov: 32)

Exomes 𝑓: 0.079 ( 5024 hom. )

Consequence

CDC73
NM_024529.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6O:1

Conservation

PhyloP100: -0.170

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 1-193249713-C-G is Benign according to our data. Variant chr1-193249713-C-G is described in ClinVar as [Benign]. Clinvar id is 21682.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0882 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDC73	NM_024529.5 link	c.1418-17C>G		intron_variant	Intron 15 of 16	ENST00000367435.5	NP_078805.3	Q6P1J9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDC73	ENST00000367435.5 link	c.1418-17C>G		intron_variant	Intron 15 of 16	1	NM_024529.5	ENSP00000356405.4		Q6P1J9

Frequencies

GnomAD3 genomes

AF:

0.0589

AC:

8936

AN:

151634

Hom.:

364

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0171

Gnomad AMI

AF:

0.161

Gnomad AMR

AF:

0.0517

Gnomad ASJ

AF:

0.0771

Gnomad EAS

AF:

0.000579

Gnomad SAS

AF:

0.0200

Gnomad FIN

AF:

0.0634

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0900

Gnomad OTH

AF:

0.0716

GnomAD3 exomes

AF:

0.0592

AC:

14789

AN:

249960

Hom.:

593

AF XY:

0.0596

AC XY:

8055

AN XY:

135222

show subpopulations

Gnomad AFR exome

AF:

0.0149

Gnomad AMR exome

AF:

0.0386

Gnomad ASJ exome

AF:

0.0779

Gnomad EAS exome

AF:

0.000218

Gnomad SAS exome

AF:

0.0187

Gnomad FIN exome

AF:

0.0600

Gnomad NFE exome

AF:

0.0901

Gnomad OTH exome

AF:

0.0648

GnomAD4 exome

AF:

0.0788

AC:

113566

AN:

1440802

Hom.:

5024

Cov.:

AF XY:

0.0776

AC XY:

55688

AN XY:

718040

show subpopulations

Gnomad4 AFR exome

AF:

0.0127

Gnomad4 AMR exome

AF:

0.0397

Gnomad4 ASJ exome

AF:

0.0792

Gnomad4 EAS exome

AF:

0.000203

Gnomad4 SAS exome

AF:

0.0211

Gnomad4 FIN exome

AF:

0.0609

Gnomad4 NFE exome

AF:

0.0914

Gnomad4 OTH exome

AF:

0.0683

GnomAD4 genome

AF:

0.0589

AC:

8936

AN:

151750

Hom.:

364

Cov.:

AF XY:

0.0568

AC XY:

4216

AN XY:

74178

show subpopulations

Gnomad4 AFR

AF:

0.0170

Gnomad4 AMR

AF:

0.0516

Gnomad4 ASJ

AF:

0.0771

Gnomad4 EAS

AF:

0.000580

Gnomad4 SAS

AF:

0.0200

Gnomad4 FIN

AF:

0.0634

Gnomad4 NFE

AF:

0.0901

Gnomad4 OTH

AF:

0.0704

Alfa

AF:

0.0481

Hom.:

Bravo

AF:

0.0572

Asia WGS

AF:

0.00982

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Apr 28, 2016

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant summary: c.1418-17C>G in the CDC73 gene is an intronic change that involves a non-conserved nucleotide. 5/5 programs in Alamut predict that this variant does not affect normal splicing, however no functional studies supporting this notion were published at the time of evaluation. The variant is present in the control population dataset of ExAC at frequency of 5.97%, including numerous homozygous occurrences. The observed frequency greatly exceeds the maximum expected allele frequency for a pathogenic variant of 0.0004%, suggesting that it is a benign polymorphism. The variant of interest has been reported as Benign/Polymorphism by a reputable database and published reports (Newey, 2010; Frank-Raue, 2011). Taking together, based on the prevalence of this variant in general population the variant was classified as Benign. -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Parathyroid carcinoma

Benign:1Other:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

GeneReviews

Significance: not provided

Review Status: no classification provided

Collection Method: literature only

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hyperparathyroidism 2 with jaw tumors

Benign:1

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance: 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

-0.85

CADD

Benign

0.97

DANN

Benign

0.39

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over