6-139373337-G-C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_006079.5(CITED2):​c.608C>G​(p.Ala203Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000206 in 1,453,434 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A203V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

CITED2
NM_006079.5 missense

Scores

1
3
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.50

Publications

0 publications found
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 Gene-Disease associations (from GenCC):
  • atrial septal defect 8
    Inheritance: AD Classification: MODERATE Submitted by: Laboratory for Molecular Medicine
  • congenital heart defects, multiple types
    Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
  • ventricular septal defect 2
    Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.31010604).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CITED2NM_006079.5 linkc.608C>G p.Ala203Gly missense_variant Exon 2 of 2 ENST00000367651.4 NP_006070.2 Q99967-1D9ZGF1
CITED2NM_001168389.3 linkc.623C>G p.Ala208Gly missense_variant Exon 2 of 2 NP_001161861.2 Q99967A0A0A0MTM3
CITED2NM_001168388.3 linkc.608C>G p.Ala203Gly missense_variant Exon 2 of 2 NP_001161860.1 Q99967-1D9ZGF1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CITED2ENST00000367651.4 linkc.608C>G p.Ala203Gly missense_variant Exon 2 of 2 1 NM_006079.5 ENSP00000356623.2 Q99967-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000206
AC:
3
AN:
1453434
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
723148
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
32842
American (AMR)
AF:
0.00
AC:
0
AN:
44164
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25950
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39070
South Asian (SAS)
AF:
0.00
AC:
0
AN:
85460
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
51252
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5750
European-Non Finnish (NFE)
AF:
0.00000271
AC:
3
AN:
1108910
Other (OTH)
AF:
0.00
AC:
0
AN:
60036
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.492
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.085
BayesDel_addAF
Benign
-0.076
T
BayesDel_noAF
Benign
-0.35
CADD
Benign
22
DANN
Benign
0.95
DEOGEN2
Benign
0.13
T;T;T
Eigen
Benign
0.070
Eigen_PC
Uncertain
0.26
FATHMM_MKL
Uncertain
0.88
D
LIST_S2
Benign
0.65
.;T;T
M_CAP
Uncertain
0.18
D
MetaRNN
Benign
0.31
T;T;T
MetaSVM
Benign
-0.96
T
MutationAssessor
Benign
1.4
L;.;L
PhyloP100
6.5
PrimateAI
Pathogenic
0.81
D
PROVEAN
Benign
-0.24
N;.;N
REVEL
Benign
0.17
Sift
Benign
0.19
T;.;T
Sift4G
Benign
0.33
T;T;T
Polyphen
0.089
B;.;B
Vest4
0.20
MutPred
0.73
Gain of catalytic residue at A203 (P = 0.0571);.;Gain of catalytic residue at A203 (P = 0.0571);
MVP
0.37
MPC
0.30
ClinPred
0.72
D
GERP RS
5.4
Varity_R
0.20
gMVP
0.44
Mutation Taster
=84/16
polymorphism

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

Other links and lift over

dbSNP: rs768243056; hg19: chr6-139694474; API