6-139373389-C-CGCCGCCCGAGCTGCTGCCAGAGCCGCCGGGGGTGCTGCT

Variant names:

• chr6-139373389-C-CGCCGCCCGAGCTGCTGCCAGAGCCGCCGGGGGTGCTGCT
• NM_006079.5:c.517_555dupAGCAGCACCCCCGGCGGCTCTGGCAGCAGCTCGGGCGGC

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP3

The NM_006079.5(CITED2):​c.517_555dupAGCAGCACCCCCGGCGGCTCTGGCAGCAGCTCGGGCGGC​(p.Gly185_Gly186insSerSerThrProGlyGlySerGlySerSerSerGlyGly) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CITED2 NM_006079.5 conservative_inframe_insertion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.704
• 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: Likely_benign. The variant received -1 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_006079.5

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.517_555dupAGCAGCACCCCCGGCGGCTCTGGCAGCAGCTCGGGCGGC	p.Gly185_Gly186insSerSerThrProGlyGlySerGlySerSerSerGlyGly	conservative_inframe_insertion	Exon 2 of 2	NP_006070.2
	CITED2	NM_001168389.3		c.532_570dupAGCAGCACCCCCGGCGGCTCTGGCAGCAGCTCGGGCGGC	p.Gly190_Gly191insSerSerThrProGlyGlySerGlySerSerSerGlyGly	conservative_inframe_insertion	Exon 2 of 2	NP_001161861.2	A0A0A0MTM3
	CITED2	NM_001168388.3		c.517_555dupAGCAGCACCCCCGGCGGCTCTGGCAGCAGCTCGGGCGGC	p.Gly185_Gly186insSerSerThrProGlyGlySerGlySerSerSerGlyGly	conservative_inframe_insertion	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.517_555dupAGCAGCACCCCCGGCGGCTCTGGCAGCAGCTCGGGCGGC	p.Gly185_Gly186insSerSerThrProGlyGlySerGlySerSerSerGlyGly	conservative_inframe_insertion	Exon 2 of 2	ENSP00000356623.2	Q99967-1
	CITED2	ENST00000537332.2	TSL:3	c.532_570dupAGCAGCACCCCCGGCGGCTCTGGCAGCAGCTCGGGCGGC	p.Gly190_Gly191insSerSerThrProGlyGlySerGlySerSerSerGlyGly	conservative_inframe_insertion	Exon 2 of 2	ENSP00000444198.2	A0A0A0MTM3
	CITED2	ENST00000536159.2	TSL:3	c.517_555dupAGCAGCACCCCCGGCGGCTCTGGCAGCAGCTCGGGCGGC	p.Gly185_Gly186insSerSerThrProGlyGlySerGlySerSerSerGlyGly	conservative_inframe_insertion	Exon 2 of 2	ENSP00000442831.1	Q99967-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	CITED2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.70

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr6-139694526;