Variant 6-139373251-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_006079.5(CITED2):c.694G>A(p.Val232Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CITED2
NM_006079.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.50

Variant links:

Genes affected

CITED2 (HGNC:1987): (Cbp/p300 interacting transactivator with Glu/Asp rich carboxy-terminal domain 2) The protein encoded by this gene inhibits transactivation of HIF1A-induced genes by competing with binding of hypoxia-inducible factor 1-alpha to p300-CH1. Mutations in this gene are a cause of cardiac septal defects. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, May 2012]

CITED2 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.848

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CITED2	NM_006079.5 linkuse as main transcript	c.694G>A	p.Val232Met	missense_variant	2/2	ENST00000367651.4	NP_006070.2
CITED2	NM_001168389.3 linkuse as main transcript	c.709G>A	p.Val237Met	missense_variant	2/2		NP_001161861.2
CITED2	NM_001168388.3 linkuse as main transcript	c.694G>A	p.Val232Met	missense_variant	2/2		NP_001161860.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CITED2	ENST00000367651.4 linkuse as main transcript	c.694G>A	p.Val232Met	missense_variant	2/2	1	NM_006079.5	ENSP00000356623	P1	Q99967-1
	ENST00000650173.1 linkuse as main transcript	n.510-55830C>T		intron_variant, non_coding_transcript_variant
CITED2	ENST00000537332.2 linkuse as main transcript	c.709G>A	p.Val237Met	missense_variant	2/2	3		ENSP00000444198
CITED2	ENST00000536159.2 linkuse as main transcript	c.694G>A	p.Val232Met	missense_variant	2/2	3		ENSP00000442831	P1	Q99967-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461862

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727226

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:

8.99e-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

Revvity Omics, Revvity

Oct 29, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

1.0

BayesDel_addAF

Pathogenic

0.32

BayesDel_noAF

Pathogenic

0.23

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.60

D;T;D;.

Eigen

Pathogenic

0.70

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.96

.;D;D;D

M_CAP

Benign

0.041

MetaRNN

Pathogenic

0.85

D;D;D;D

MetaSVM

Benign

-0.42

MutationAssessor

Benign

1.8

L;.;L;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.78

PROVEAN

Uncertain

-2.6

D;.;D;.

REVEL

Uncertain

0.61

Sift

Uncertain

0.0010

D;.;D;.

Sift4G

Uncertain

0.0040

D;D;D;D

Polyphen

1.0

D;.;D;.

Vest4

0.82

MutPred

0.64

Loss of catalytic residue at V232 (P = 0.1399);.;Loss of catalytic residue at V232 (P = 0.1399);.;

MVP

0.80

MPC

1.0

ClinPred

0.98

GERP RS

5.7

Varity_R

0.79

gMVP

0.91

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

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