Variant 2-27217629-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000264705.9(CAD):c.78A>G(p.Glu26=) variant causes a synonymous change. The variant allele was found at a frequency of 0.000000688 in 1,453,842 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

CAD
ENST00000264705.9 synonymous

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.56

Variant links:

Genes affected

CAD (HGNC:1424): (carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase) The de novo synthesis of pyrimidine nucleotides is required for mammalian cells to proliferate. This gene encodes a trifunctional protein which is associated with the enzymatic activities of the first 3 enzymes in the 6-step pathway of pyrimidine biosynthesis: carbamoylphosphate synthetase (CPS II), aspartate transcarbamoylase, and dihydroorotase. This protein is regulated by the mitogen-activated protein kinase (MAPK) cascade, which indicates a direct link between activation of the MAPK cascade and de novo biosynthesis of pyrimidine nucleotides. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Apr 2015]

CAD links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CAD	NM_004341.5 linkuse as main transcript	c.78A>G	p.Glu26=	synonymous_variant	1/44	ENST00000264705.9	NP_004332.2
CAD	NM_001306079.2 linkuse as main transcript	c.78A>G	p.Glu26=	synonymous_variant	1/43		NP_001293008.1
CAD	XM_047445803.1 linkuse as main transcript	c.78A>G	p.Glu26=	synonymous_variant	1/45		XP_047301759.1
CAD	XM_006712101.4 linkuse as main transcript	c.78A>G	p.Glu26=	synonymous_variant	1/44		XP_006712164.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAD	ENST00000264705.9 linkuse as main transcript	c.78A>G	p.Glu26=	synonymous_variant	1/44	1	NM_004341.5	ENSP00000264705	P1
CAD	ENST00000403525.5 linkuse as main transcript	c.78A>G	p.Glu26=	synonymous_variant	1/43	1		ENSP00000384510

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.88e-7

AC:

AN:

1453842

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

722632

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.02e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Oct 03, 2023

This sequence change affects codon 26 of the CAD mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the CAD protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CAD-related conditions. ClinVar contains an entry for this variant (Variation ID: 1431446). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Uncertain

DANN

Benign

0.91

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.86

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.86

Position offset: 0

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over