chr6-139373359-TGCCGCC-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP3 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
• congenital heart disease

  Inheritance: AD Classification: MODERATE Submitted by: ClinGen
• ventricular septal defect 2

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ENSG00000226571 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_006079.5
• 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 VariationId is 3350409.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 209 AD,Unknown gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006079.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CITED2	NM_006079.5	MANE Select	c.580_585delGGCGGC	p.Gly194_Gly195del	conservative_inframe_deletion	Exon 2 of 2	NP_006070.2
	CITED2	NM_001168389.3		c.595_600delGGCGGC	p.Gly199_Gly200del	conservative_inframe_deletion	Exon 2 of 2	NP_001161861.2	A0A0A0MTM3
	CITED2	NM_001168388.3		c.580_585delGGCGGC	p.Gly194_Gly195del	conservative_inframe_deletion	Exon 2 of 2	NP_001161860.1	Q99967-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CITED2	ENST00000367651.4	TSL:1 MANE Select	c.580_585delGGCGGC	p.Gly194_Gly195del	conservative_inframe_deletion	Exon 2 of 2	ENSP00000356623.2	Q99967-1
	CITED2	ENST00000537332.2	TSL:3	c.595_600delGGCGGC	p.Gly199_Gly200del	conservative_inframe_deletion	Exon 2 of 2	ENSP00000444198.2	A0A0A0MTM3
	CITED2	ENST00000536159.2	TSL:3	c.580_585delGGCGGC	p.Gly194_Gly195del	conservative_inframe_deletion	Exon 2 of 2	ENSP00000442831.1	Q99967-1

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

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	CITED2-related disorder (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

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;