6-139373363-G-A

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_006079.5(CITED2):​c.582C>T​(p.Gly194Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00373 in 1,582,560 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0024 ( 2 hom., cov: 32)
Exomes 𝑓: 0.0039 ( 14 hom. )

Consequence

CITED2
NM_006079.5 synonymous

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.951
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.65).
BP6
Variant 6-139373363-G-A is Benign according to our data. Variant chr6-139373363-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 717442.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-139373363-G-A is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=0.951 with no splicing effect.
BS2
High AC in GnomAd4 at 367 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CITED2NM_006079.5 linkc.582C>T p.Gly194Gly synonymous_variant Exon 2 of 2 ENST00000367651.4 NP_006070.2 Q99967-1D9ZGF1
CITED2NM_001168389.3 linkc.597C>T p.Gly199Gly synonymous_variant Exon 2 of 2 NP_001161861.2 Q99967A0A0A0MTM3
CITED2NM_001168388.3 linkc.582C>T p.Gly194Gly synonymous_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.582C>T p.Gly194Gly synonymous_variant Exon 2 of 2 1 NM_006079.5 ENSP00000356623.2 Q99967-1
CITED2ENST00000537332.2 linkc.597C>T p.Gly199Gly synonymous_variant Exon 2 of 2 3 ENSP00000444198.2 A0A0A0MTM3
CITED2ENST00000536159.2 linkc.582C>T p.Gly194Gly synonymous_variant Exon 2 of 2 3 ENSP00000442831.1 Q99967-1
ENSG00000226571ENST00000650173.1 linkn.510-55718G>A intron_variant Intron 4 of 7

Frequencies

GnomAD3 genomes
AF:
0.00242
AC:
367
AN:
151580
Hom.:
2
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000750
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00322
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.000473
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00404
Gnomad OTH
AF:
0.00336
GnomAD3 exomes
AF:
0.00221
AC:
473
AN:
214128
Hom.:
1
AF XY:
0.00208
AC XY:
249
AN XY:
119770
show subpopulations
Gnomad AFR exome
AF:
0.000643
Gnomad AMR exome
AF:
0.00260
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000737
Gnomad FIN exome
AF:
0.000945
Gnomad NFE exome
AF:
0.00355
Gnomad OTH exome
AF:
0.00195
GnomAD4 exome
AF:
0.00387
AC:
5536
AN:
1430872
Hom.:
14
Cov.:
31
AF XY:
0.00379
AC XY:
2701
AN XY:
712070
show subpopulations
Gnomad4 AFR exome
AF:
0.000568
Gnomad4 AMR exome
AF:
0.00240
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000678
Gnomad4 FIN exome
AF:
0.000657
Gnomad4 NFE exome
AF:
0.00467
Gnomad4 OTH exome
AF:
0.00359
GnomAD4 genome
AF:
0.00242
AC:
367
AN:
151688
Hom.:
2
Cov.:
32
AF XY:
0.00237
AC XY:
176
AN XY:
74198
show subpopulations
Gnomad4 AFR
AF:
0.000747
Gnomad4 AMR
AF:
0.00321
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000414
Gnomad4 FIN
AF:
0.000473
Gnomad4 NFE
AF:
0.00404
Gnomad4 OTH
AF:
0.00333
Alfa
AF:
0.000923
Hom.:
0
Bravo
AF:
0.00254

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Jun 01, 2024
CeGaT Center for Human Genetics Tuebingen
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

CITED2: BP4, BP7, BS2 -

Dec 31, 2019
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

CITED2-related disorder Benign:1
Jan 03, 2020
PreventionGenetics, part of Exact Sciences
Significance: Likely benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.65
CADD
Benign
7.0
DANN
Benign
0.93

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs530008417; hg19: chr6-139694500; API