Genetic Variant CDC73:c.237+29_237+32delCTAT (chr1-193125238-TTATC-T) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_024529.5(CDC73):c.237+29_237+32delCTAT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0474 in 1,331,598 control chromosomes in the GnomAD database, including 5,691 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.047 ( 734 hom., cov: 32)

Exomes 𝑓: 0.047 ( 4957 hom. )

Consequence

CDC73
NM_024529.5 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.263

Publications

3 publications found

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 Gene-Disease associations (from GenCC):

hyperparathyroidism 2 with jaw tumors
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen, Ambry Genetics
hyperparathyroidism 1
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
parathyroid gland carcinoma
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
familial isolated hyperparathyroidism
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

CDC73 links:

ENSG00000308280 (HGNC:):

ENSG00000308280 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP6

Variant 1-193125238-TTATC-T is Benign according to our data. Variant chr1-193125238-TTATC-T is described in ClinVar as Benign. ClinVar VariationId is 21684.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.465 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDC73	NM_024529.5 link	c.237+29_237+32delCTAT		intron_variant	Intron 2 of 16	ENST00000367435.5	NP_078805.3	Q6P1J9
CDC73	XM_006711537.5 link	c.237+29_237+32delCTAT		intron_variant	Intron 2 of 10		XP_006711600.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDC73	ENST00000367435.5 link	c.237+22_237+25delTATC		intron_variant	Intron 2 of 16	1	NM_024529.5	ENSP00000356405.4		Q6P1J9

Frequencies

GnomAD3 genomes

AF:

0.0474

AC:

7209

AN:

152160

Hom.:

735

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0104

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0702

Gnomad ASJ

AF:

0.0320

Gnomad EAS

AF:

0.481

Gnomad SAS

AF:

0.0821

Gnomad FIN

AF:

0.0588

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0290

Gnomad OTH

AF:

0.0468

GnomAD2 exomes

AF:

0.0830

AC:

20784

AN:

250312

AF XY:

0.0794

show subpopulations

Gnomad AFR exome

AF:

0.00947

Gnomad AMR exome

AF:

0.124

Gnomad ASJ exome

AF:

0.0325

Gnomad EAS exome

AF:

0.492

Gnomad FIN exome

AF:

0.0601

Gnomad NFE exome

AF:

0.0291

Gnomad OTH exome

AF:

0.0602

GnomAD4 exome

AF:

0.0474

AC:

55937

AN:

1179320

Hom.:

4957

AF XY:

0.0483

AC XY:

29022

AN XY:

601002

show subpopulations

African (AFR)

AF:

0.00723

AC:

202

AN:

27920

American (AMR)

AF:

0.122

AC:

5406

AN:

44324

Ashkenazi Jewish (ASJ)

AF:

0.0318

AC:

777

AN:

24426

East Asian (EAS)

AF:

0.438

AC:

16637

AN:

37998

South Asian (SAS)

AF:

0.0685

AC:

5509

AN:

80384

European-Finnish (FIN)

AF:

0.0553

AC:

2944

AN:

53236

Middle Eastern (MID)

AF:

0.0422

AC:

220

AN:

5210

European-Non Finnish (NFE)

AF:

0.0250

AC:

21387

AN:

854718

Other (OTH)

AF:

0.0559

AC:

2855

AN:

51104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

2290

4581

6871

9162

11452

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

878

1756

2634

3512

4390

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0473

AC:

7200

AN:

152278

Hom.:

734

Cov.:

AF XY:

0.0520

AC XY:

3871

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.0104

AC:

432

AN:

41576

American (AMR)

AF:

0.0704

AC:

1078

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0320

AC:

111

AN:

3472

East Asian (EAS)

AF:

0.481

AC:

2479

AN:

5152

South Asian (SAS)

AF:

0.0815

AC:

393

AN:

4822

European-Finnish (FIN)

AF:

0.0588

AC:

624

AN:

10610

Middle Eastern (MID)

AF:

0.0442

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0290

AC:

1973

AN:

68022

Other (OTH)

AF:

0.0459

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

283

565

848

1130

1413

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

184

276

368

460

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0380

Hom.:

Bravo

AF:

0.0507

Asia WGS

AF:

0.222

AC:

773

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 04, 2025

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.26

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over