6-139373408-A-AGAGCCGCCGGGGGTGCTGCTGCCGCCC

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BS2_Supporting

The NM_006079.5(CITED2):c.510_536dupGGGCGGCAGCAGCACCCCCGGCGGCTC(p.Ser179_Gly180insGlyGlySerSerThrProGlyGlySer) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000027 in 1,553,708 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

CITED2
NM_006079.5 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 2.07

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 -1 ACMG points.

BS2

High AC in GnomAd4 at 5 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CITED2	NM_006079.5 link	c.510_536dupGGGCGGCAGCAGCACCCCCGGCGGCTC	p.Ser179_Gly180insGlyGlySerSerThrProGlyGlySer	disruptive_inframe_insertion	Exon 2 of 2	ENST00000367651.4	NP_006070.2	Q99967-1D9ZGF1
CITED2	NM_001168389.3 link	c.525_551dupGGGCGGCAGCAGCACCCCCGGCGGCTC	p.Ser184_Gly185insGlyGlySerSerThrProGlyGlySer	disruptive_inframe_insertion	Exon 2 of 2		NP_001161861.2	Q99967A0A0A0MTM3
CITED2	NM_001168388.3 link	c.510_536dupGGGCGGCAGCAGCACCCCCGGCGGCTC	p.Ser179_Gly180insGlyGlySerSerThrProGlyGlySer	disruptive_inframe_insertion	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.510_536dupGGGCGGCAGCAGCACCCCCGGCGGCTC	p.Ser179_Gly180insGlyGlySerSerThrProGlyGlySer	disruptive_inframe_insertion	Exon 2 of 2	1	NM_006079.5	ENSP00000356623.2	Q99967-1
CITED2	ENST00000537332.2 link	c.525_551dupGGGCGGCAGCAGCACCCCCGGCGGCTC	p.Ser184_Gly185insGlyGlySerSerThrProGlyGlySer	disruptive_inframe_insertion	Exon 2 of 2	3		ENSP00000444198.2	A0A0A0MTM3
CITED2	ENST00000536159.2 link	c.510_536dupGGGCGGCAGCAGCACCCCCGGCGGCTC	p.Ser179_Gly180insGlyGlySerSerThrProGlyGlySer	disruptive_inframe_insertion	Exon 2 of 2	3		ENSP00000442831.1	Q99967-1
ENSG00000226571	ENST00000650173.1 link	n.510-55646_510-55620dupCGAGCCGCCGGGGGTGCTGCTGCCGCC		intron_variant	Intron 4 of 7

Frequencies

GnomAD3 genomes

AF:

0.0000399

AC:

AN:

150206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000982

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000212

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000210

AC:

AN:

190406

Hom.:

AF XY:

0.0000189

AC XY:

AN XY:

106090

show subpopulations

Gnomad AFR exome

AF:

0.0000980

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000884

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000113

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000264

AC:

AN:

1403390

Hom.:

Cov.:

AF XY:

0.0000301

AC XY:

AN XY:

697196

show subpopulations

Gnomad4 AFR exome

AF:

0.0000668

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000129

Gnomad4 FIN exome

AF:

0.0000203

Gnomad4 NFE exome

AF:

0.0000230

Gnomad4 OTH exome

AF:

0.000139

GnomAD4 genome

AF:

0.0000333

AC:

AN:

150318

Hom.:

Cov.:

AF XY:

0.0000272

AC XY:

AN XY:

73440

show subpopulations

Gnomad4 AFR

AF:

0.0000979

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000148

Gnomad4 OTH

AF:

0.00

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CITED2-related disorder

Uncertain:1

Oct 20, 2023

PreventionGenetics, part of Exact Sciences

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

The CITED2 c.525_551dup27 variant is predicted to result in an in-frame duplication (p.Gly177_Gly185dup). To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0098% of alleles in individuals of African descent in gnomAD; however, this variant is located in a low complexity region and frequency estimates may not be reliable (http://gnomad.broadinstitute.org/variant/6-139694545-A-AGAGCCGCCGGGGGTGCTGCTGCCGCCC). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

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