Variant 6-139373356-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_006079.5(CITED2):c.589G>C(p.Gly197Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000695 in 1,439,652 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

CITED2
NM_006079.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.475

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.40571514).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CITED2	NM_006079.5 linkuse as main transcript	c.589G>C	p.Gly197Arg	missense_variant	2/2	ENST00000367651.4	NP_006070.2
CITED2	NM_001168389.3 linkuse as main transcript	c.604G>C	p.Gly202Arg	missense_variant	2/2		NP_001161861.2
CITED2	NM_001168388.3 linkuse as main transcript	c.589G>C	p.Gly197Arg	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.589G>C	p.Gly197Arg	missense_variant	2/2	1	NM_006079.5	ENSP00000356623	P1	Q99967-1
	ENST00000650173.1 linkuse as main transcript	n.510-55725C>G		intron_variant, non_coding_transcript_variant
CITED2	ENST00000537332.2 linkuse as main transcript	c.604G>C	p.Gly202Arg	missense_variant	2/2	3		ENSP00000444198
CITED2	ENST00000536159.2 linkuse as main transcript	c.589G>C	p.Gly197Arg	missense_variant	2/2	3		ENSP00000442831	P1	Q99967-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.95e-7

AC:

AN:

1439652

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

716244

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:

9.06e-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

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 15, 2023

The c.589G>C (p.G197R) alteration is located in exon 2 (coding exon 1) of the CITED2 gene. This alteration results from a G to C substitution at nucleotide position 589, causing the glycine (G) at amino acid position 197 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.39

BayesDel_addAF

Uncertain

0.037

BayesDel_noAF

Benign

-0.18

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.13

T;T;T

Eigen

Benign

-0.074

Eigen_PC

Benign

-0.11

FATHMM_MKL

Benign

0.080

LIST_S2

Benign

0.53

.;T;T

M_CAP

Pathogenic

0.65

MetaRNN

Benign

0.41

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

L;.;L

MutationTaster

Benign

0.84

N;N;N

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-0.58

N;.;N

REVEL

Uncertain

0.34

Sift

Benign

0.17

T;.;T

Sift4G

Benign

0.51

T;T;T

Polyphen

0.99

D;.;D

Vest4

0.31

MutPred

0.65

Gain of MoRF binding (P = 0.0532);.;Gain of MoRF binding (P = 0.0532);

MVP

0.71

MPC

0.37

ClinPred

0.43

GERP RS

3.1

Varity_R

0.18

gMVP

0.20

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