Genetic Variant CITED2:p.Gly194_Gly195del (chr6-139373359-TGCCGCC-T) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6BS2

The NM_006079.5(CITED2):c.580_585delGGCGGC(p.Gly194_Gly195del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00252 in 1,591,230 control chromosomes in the GnomAD database, including 8 homozygotes. Variant has been reported in ClinVar as Benign (no stars). Synonymous variant affecting the same amino acid position (i.e. G194G) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0026 ( 8 hom. )

Consequence

CITED2
NM_006079.5 conservative_inframe_deletion

Scores

Not classified

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.99

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:

ENSG00000226571 (HGNC:):

ENSG00000226571 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP6

Variant 6-139373359-TGCCGCC-T is Benign according to our data. Variant chr6-139373359-TGCCGCC-T is described in ClinVar as [Benign]. Clinvar id is 3350409.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr6-139373359-TGCCGCC-T is described in Lovd as [Benign].

BS2

High AC in GnomAd4 at 209 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CITED2	NM_006079.5 link	c.580_585delGGCGGC	p.Gly194_Gly195del	conservative_inframe_deletion	Exon 2 of 2	ENST00000367651.4	NP_006070.2	Q99967-1D9ZGF1
CITED2	NM_001168389.3 link	c.595_600delGGCGGC	p.Gly199_Gly200del	conservative_inframe_deletion	Exon 2 of 2		NP_001161861.2	Q99967A0A0A0MTM3
CITED2	NM_001168388.3 link	c.580_585delGGCGGC	p.Gly194_Gly195del	conservative_inframe_deletion	Exon 2 of 2		NP_001161860.1	Q99967-1D9ZGF1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CITED2	ENST00000367651.4 link	c.580_585delGGCGGC	p.Gly194_Gly195del	conservative_inframe_deletion	Exon 2 of 2	1	NM_006079.5	ENSP00000356623.2	Q99967-1
CITED2	ENST00000537332.2 link	c.595_600delGGCGGC	p.Gly199_Gly200del	conservative_inframe_deletion	Exon 2 of 2	3		ENSP00000444198.2	A0A0A0MTM3
CITED2	ENST00000536159.2 link	c.580_585delGGCGGC	p.Gly194_Gly195del	conservative_inframe_deletion	Exon 2 of 2	3		ENSP00000442831.1	Q99967-1
ENSG00000226571	ENST00000650173.1 link	n.510-55716_510-55711delCGCCGC		intron_variant	Intron 4 of 7

Frequencies

GnomAD3 genomes

AF:

0.00138

AC:

209

AN:

151932

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000721

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00252

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00127

AC:

271

AN:

213768

Hom.:

AF XY:

0.00125

AC XY:

150

AN XY:

119786

show subpopulations

Gnomad AFR exome

AF:

0.000644

Gnomad AMR exome

AF:

0.000475

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000211

Gnomad NFE exome

AF:

0.00247

Gnomad OTH exome

AF:

0.00253

GnomAD4 exome

AF:

0.00264

AC:

3793

AN:

1439190

Hom.:

AF XY:

0.00252

AC XY:

1804

AN XY:

716038

show subpopulations

Gnomad4 AFR exome

AF:

0.000377

Gnomad4 AMR exome

AF:

0.000511

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000475

Gnomad4 FIN exome

AF:

0.000288

Gnomad4 NFE exome

AF:

0.00322

Gnomad4 OTH exome

AF:

0.00317

GnomAD4 genome

AF:

0.00137

AC:

209

AN:

152040

Hom.:

Cov.:

AF XY:

0.00135

AC XY:

100

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.000482

Gnomad4 AMR

AF:

0.000720

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.00252

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.000510

Hom.:

Bravo

AF:

0.00156

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CITED2-related disorder

Benign:1

Mar 26, 2024

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as 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

Splicing

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over