rs4466634

Variant names:

• chr1-193125245-T-A
• rs4466634
• NM_024529.5:c.237+28T>A

Your query was ambiguous. Multiple possible variants found:

• chr1-193125245-T-A
• chr1-193125245-T-C
• chr1-193125245-T-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_024529.5(CDC73):​c.237+28T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CDC73 NM_024529.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.05
• Publications: 11 publications found

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

ENSG00000308280 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDC73	NM_024529.5	c.237+28T>A		intron_variant	Intron 2 of 16	ENST00000367435.5	NP_078805.3
CDC73	XM_006711537.5	c.237+28T>A		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	c.237+28T>A		intron_variant	Intron 2 of 16	1	NM_024529.5	ENSP00000356405.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1082722 Hom.: 0 Cov.: 15 AF XY: 0.00 AC XY: 0 AN XY: 556558

African (AFR) AF: 0.00 AC: 0 AN: 26000

American (AMR) AF: 0.00 AC: 0 AN: 44200

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23856

East Asian (EAS) AF: 0.00 AC: 0 AN: 37868

South Asian (SAS) AF: 0.00 AC: 0 AN: 78556

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53136

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5020

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 765910

Other (OTH) AF: 0.00 AC: 0 AN: 48176

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.1
DANN	Benign	0.60
PhyloP100		1.1

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

Other links and lift over

dbSNP: rs4466634; hg19: chr1-193094375;