Variant 1-193142098-TGAGAGAGA-TGAGAGA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_024529.5(CDC73):c.729+50_729+51delAG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0154 in 147,604 control chromosomes in the GnomAD database, including 27 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 27 hom., cov: 32)

Exomes 𝑓: 0.17 ( 112 hom. )

Failed GnomAD Quality Control

Consequence

CDC73
NM_024529.5 intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

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:

CDC73 (HGNC:):

CDC73 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 1-193142098-TGA-T is Benign according to our data. Variant chr1-193142098-TGA-T is described in ClinVar as [Likely_benign]. Clinvar id is 21686.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0154 (2274/147604) while in subpopulation NFE AF= 0.0245 (1630/66416). AF 95% confidence interval is 0.0236. There are 27 homozygotes in gnomad4. There are 1047 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2274 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDC73	NM_024529.5 linkuse as main transcript	c.729+50_729+51delAG		intron_variant		ENST00000367435.5	NP_078805.3	Q6P1J9
CDC73	XM_006711537.5 linkuse as main transcript	c.729+50_729+51delAG		intron_variant			XP_006711600.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDC73	ENST00000367435.5 linkuse as main transcript	c.729+50_729+51delAG		intron_variant		1	NM_024529.5	ENSP00000356405.4		Q6P1J9

Frequencies

GnomAD3 genomes

AF:

0.0154

AC:

2274

AN:

147540

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00420

Gnomad AMI

AF:

0.0929

Gnomad AMR

AF:

0.0106

Gnomad ASJ

AF:

0.00176

Gnomad EAS

AF:

0.000195

Gnomad SAS

AF:

0.00340

Gnomad FIN

AF:

0.0202

Gnomad MID

AF:

0.00645

Gnomad NFE

AF:

0.0245

Gnomad OTH

AF:

0.00938

GnomAD4 exome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.167

AC:

160078

AN:

958856

Hom.:

112

AF XY:

0.176

AC XY:

82555

AN XY:

469022

show subpopulations

Gnomad4 AFR exome

AF:

0.177

Gnomad4 AMR exome

AF:

0.295

Gnomad4 ASJ exome

AF:

0.247

Gnomad4 EAS exome

AF:

0.249

Gnomad4 SAS exome

AF:

0.275

Gnomad4 FIN exome

AF:

0.230

Gnomad4 NFE exome

AF:

0.150

Gnomad4 OTH exome

AF:

0.188

GnomAD4 genome

AF:

0.0154

AC:

2274

AN:

147604

Hom.:

Cov.:

AF XY:

0.0146

AC XY:

1047

AN XY:

71824

show subpopulations

Gnomad4 AFR

AF:

0.00419

Gnomad4 AMR

AF:

0.0106

Gnomad4 ASJ

AF:

0.00176

Gnomad4 EAS

AF:

0.000196

Gnomad4 SAS

AF:

0.00341

Gnomad4 FIN

AF:

0.0202

Gnomad4 NFE

AF:

0.0245

Gnomad4 OTH

AF:

0.00930

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Aug 15, 2023

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 15, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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