6-139373408-AGAGCCGCCGGGGGTGCTGCTGCCGCCC-A

Position:

• chr6-139373408-AGAGCCGCCGGGGGTGCTGCTGCCGCCC-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PP5 BS2_Supporting

The NM_006079.5(CITED2):​c.510_536del​(p.Gly172_Gly180del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000174 in 1,553,684 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency:
  • Genomes: 𝑓 0.00018 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00017 (0 hom.)
• Consequence: CITED2 NM_006079.5 inframe_deletion
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 2.34

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]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PP5: Variant 6-139373408-AGAGCCGCCGGGGGTGCTGCTGCCGCCC-A is Pathogenic according to our data. Variant chr6-139373408-AGAGCCGCCGGGGGTGCTGCTGCCGCCC-A is described in ClinVar as [Pathogenic]. Clinvar id is 6721.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High AC in GnomAd4 at 27 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/exons	MANE	Protein	UniProt
CITED2	NM_006079.5	c.510_536del	p.Gly172_Gly180del	inframe_deletion	2/2	ENST00000367651.4	NP_006070.2
CITED2	NM_001168388.3	c.510_536del	p.Gly172_Gly180del	inframe_deletion	2/2		NP_001161860.1
CITED2	NM_001168389.3	c.525_551del	p.Gly177_Gly185del	inframe_deletion	2/2		NP_001161861.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CITED2	ENST00000367651.4	c.510_536del	p.Gly172_Gly180del	inframe_deletion	2/2	1	NM_006079.5	ENSP00000356623	P1
	ENST00000650173.1	n.510-55646_510-55620del		intron_variant, non_coding_transcript_variant
CITED2	ENST00000536159.2	c.510_536del	p.Gly172_Gly180del	inframe_deletion	2/2	3		ENSP00000442831	P1
CITED2	ENST00000537332.2	c.525_551del	p.Gly177_Gly185del	inframe_deletion	2/2	3		ENSP00000444198

Frequencies

GnomAD3 genomes AF: 0.000180 AC: 27 AN: 150200 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000491

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000397

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000198

Gnomad SAS AF: 0.000636

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000193

Gnomad OTH AF: 0.000970

GnomAD3 exomes AF: 0.000142 AC: 27 AN: 190406 Hom.: 1 AF XY: 0.0000943 AC XY: 10 AN XY: 106090

Gnomad AFR exome AF: 0.0000980

Gnomad AMR exome AF: 0.000351

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000146

Gnomad SAS exome AF: 0.0000884

Gnomad FIN exome AF: 0.000105

Gnomad NFE exome AF: 0.000125

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000173 AC: 243 AN: 1403372 Hom.: 0 AF XY: 0.000176 AC XY: 123 AN XY: 697184

Gnomad4 AFR exome AF: 0.000200

Gnomad4 AMR exome AF: 0.000328

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000137

Gnomad4 SAS exome AF: 0.000181

Gnomad4 FIN exome AF: 0.0000407

Gnomad4 NFE exome AF: 0.000176

Gnomad4 OTH exome AF: 0.000208

GnomAD4 genome AF: 0.000180 AC: 27 AN: 150312 Hom.: 0 Cov.: 32 AF XY: 0.000191 AC XY: 14 AN XY: 73438

Gnomad4 AFR AF: 0.0000489

Gnomad4 AMR AF: 0.000397

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000198

Gnomad4 SAS AF: 0.000636

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000193

Gnomad4 OTH AF: 0.000960

Alfa AF: 0.0000965 Hom.: 0

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Ventricular septal defect 2 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Dec 01, 2005

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs779637348; hg19: chr6-139694545;