6-139373359-TGCCGCC-T

Variant names:

• chr6-139373359-TGCCGCC-T
• rs752543125
• NM_006079.5:c.580_585delGGCGGC

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_Moderate BS2

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 Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. G194G) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0014 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0026 (8 hom.)
• Consequence: CITED2 NM_006079.5 conservative_inframe_deletion
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 1.99
• Publications: 0 publications found

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)

ENSG00000226571 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP6: Variant 6-139373359-TGCCGCC-T is Benign according to our data. Variant chr6-139373359-TGCCGCC-T is described in ClinVar as [Likely_benign]. Clinvar id is 3350409.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 209 AD,Unknown gene.

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CITED2	ENST00000367651.4	c.580_585delGGCGGC	p.Gly194_Gly195del	conservative_inframe_deletion	Exon 2 of 2	1	NM_006079.5	ENSP00000356623.2

Frequencies

GnomAD3 genomes AF: 0.00138 AC: 209 AN: 151932 Hom.: 0 Cov.: 32

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

GnomAD2 exomes AF: 0.00127 AC: 271 AN: 213768 AF XY: 0.00125

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 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.: 8 AF XY: 0.00252 AC XY: 1804 AN XY: 716038

African (AFR) AF: 0.000377 AC: 12 AN: 31790

American (AMR) AF: 0.000511 AC: 22 AN: 43022

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25584

East Asian (EAS) AF: 0.00 AC: 0 AN: 38144

South Asian (SAS) AF: 0.0000475 AC: 4 AN: 84260

European-Finnish (FIN) AF: 0.000288 AC: 14 AN: 48630

Middle Eastern (MID) AF: 0.000350 AC: 2 AN: 5710

European-Non Finnish (NFE) AF: 0.00322 AC: 3551 AN: 1102812

Other (OTH) AF: 0.00317 AC: 188 AN: 59238

GnomAD4 genome AF: 0.00137 AC: 209 AN: 152040 Hom.: 0 Cov.: 32 AF XY: 0.00135 AC XY: 100 AN XY: 74338

African (AFR) AF: 0.000482 AC: 20 AN: 41490

American (AMR) AF: 0.000720 AC: 11 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.000189 AC: 2 AN: 10582

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00252 AC: 171 AN: 67908

Other (OTH) AF: 0.00237 AC: 5 AN: 2114

Alfa AF: 0.000510 Hom.: 0

Bravo AF: 0.00156

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

CITED2: BS1 -

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
PhyloP100		2.0
Mutation Taster		=193/7	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs752543125; hg19: chr6-139694496;