dbSNP rs10754052: CDC73:c.972+18672T>C (chr1-193171116-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_024529.5(CDC73):c.972+18672T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.724 in 152,116 control chromosomes in the GnomAD database, including 40,129 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.72 ( 40129 hom., cov: 32)

Consequence

CDC73
NM_024529.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.68

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.01).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.798 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDC73	NM_024529.5 link	c.972+18672T>C		intron_variant	Intron 10 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.972+18672T>C		intron_variant	Intron 10 of 16	1	NM_024529.5	ENSP00000356405.4		Q6P1J9

Frequencies

GnomAD3 genomes

AF:

0.724

AC:

109998

AN:

151998

Hom.:

40073

Cov.:

show subpopulations

Gnomad AFR

AF:

0.736

Gnomad AMI

AF:

0.745

Gnomad AMR

AF:

0.736

Gnomad ASJ

AF:

0.782

Gnomad EAS

AF:

0.453

Gnomad SAS

AF:

0.818

Gnomad FIN

AF:

0.669

Gnomad MID

AF:

0.766

Gnomad NFE

AF:

0.731

Gnomad OTH

AF:

0.744

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.724

AC:

110115

AN:

152116

Hom.:

40129

Cov.:

AF XY:

0.723

AC XY:

53772

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.737

AC:

30558

AN:

41482

American (AMR)

AF:

0.737

AC:

11266

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.782

AC:

2714

AN:

3472

East Asian (EAS)

AF:

0.453

AC:

2344

AN:

5176

South Asian (SAS)

AF:

0.819

AC:

3955

AN:

4830

European-Finnish (FIN)

AF:

0.669

AC:

7084

AN:

10584

Middle Eastern (MID)

AF:

0.776

AC:

228

AN:

294

European-Non Finnish (NFE)

AF:

0.732

AC:

49716

AN:

67964

Other (OTH)

AF:

0.745

AC:

1571

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1575

3151

4726

6302

7877

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

838

1676

2514

3352

4190

<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:

0.737

Hom.:

69880

Bravo

AF:

0.723

Asia WGS

AF:

0.684

AC:

2377

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.86

(source)

DANN

Benign

0.60

PhyloP100

-1.7

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over