rs150951102

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_024529.5(CDC73):c.33C>T(p.Tyr11Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00159 in 1,614,178 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00087 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0017 ( 3 hom. )

Consequence

CDC73
NM_024529.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: 1.94

Publications

1 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), Ambry Genetics, G2P, ClinGen
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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.36).

BP6

Variant 1-193122233-C-T is Benign according to our data. Variant chr1-193122233-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 241495.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.94 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000873 (133/152336) while in subpopulation NFE AF = 0.00184 (125/68034). AF 95% confidence interval is 0.00158. There are 0 homozygotes in GnomAd4. There are 59 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 133 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024529.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDC73	NM_024529.5	MANE Select	c.33C>T	p.Tyr11Tyr	synonymous	Exon 1 of 17	NP_078805.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CDC73	ENST00000367435.5	TSL:1 MANE Select	c.33C>T	p.Tyr11Tyr	synonymous	Exon 1 of 17	ENSP00000356405.4	Q6P1J9
CDC73	ENST00000958309.1		c.33C>T	p.Tyr11Tyr	synonymous	Exon 2 of 18	ENSP00000628368.1
CDC73	ENST00000958310.1		c.33C>T	p.Tyr11Tyr	synonymous	Exon 1 of 17	ENSP00000628369.1

Frequencies

GnomAD3 genomes

AF:

0.000874

AC:

133

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00184

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000640

AC:

161

AN:

251480

AF XY:

0.000662

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.00131

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.00167

AC:

2441

AN:

1461842

Hom.:

Cov.:

AF XY:

0.00159

AC XY:

1158

AN XY:

727230

show subpopulations

African (AFR)

AF:

0.000179

AC:

AN:

33476

American (AMR)

AF:

0.000134

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.000356

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00213

AC:

2370

AN:

1111986

Other (OTH)

AF:

0.000646

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

125

250

376

501

626

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

200

300

400

500

<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:

0.000873

AC:

133

AN:

152336

Hom.:

Cov.:

AF XY:

0.000792

AC XY:

AN XY:

74496

show subpopulations

African (AFR)

AF:

0.000120

AC:

AN:

41584

American (AMR)

AF:

0.0000653

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.000188

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00184

AC:

125

AN:

68034

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00101

Hom.:

Bravo

AF:

0.000786

EpiCase

AF:

0.00136

EpiControl

AF:

0.00119

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (4)

Hereditary cancer-predisposing syndrome (2)

Hyperparathyroidism 2 with jaw tumors (2)

Parathyroid carcinoma (2)

Hyperparathyroidism 1 (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Benign

0.96

PhyloP100

1.9

PromoterAI

-0.11

Neutral

(source)

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.8

Mutation Taster

=97/3

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over