6-139373389-C-CGCCGCCCGAGCTGCTGCCAGAGCCGCCGGGGGTGCTGCT

Position:

• chr6-139373389-C-CGCCGCCCGAGCTGCTGCCAGAGCCGCCGGGGGTGCTGCT

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006079.5(CITED2):​c.555_556insAGCAGCACCCCCGGCGGCTCTGGCAGCAGCTCGGGCGGC​(p.Ser173_Gly185dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CITED2 NM_006079.5 inframe_insertion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.704

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CITED2	NM_006079.5	c.555_556insAGCAGCACCCCCGGCGGCTCTGGCAGCAGCTCGGGCGGC	p.Ser173_Gly185dup	inframe_insertion	2/2	ENST00000367651.4	NP_006070.2
CITED2	NM_001168388.3	c.555_556insAGCAGCACCCCCGGCGGCTCTGGCAGCAGCTCGGGCGGC	p.Ser173_Gly185dup	inframe_insertion	2/2		NP_001161860.1
CITED2	NM_001168389.3	c.570_571insAGCAGCACCCCCGGCGGCTCTGGCAGCAGCTCGGGCGGC	p.Ser178_Gly190dup	inframe_insertion	2/2		NP_001161861.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CITED2	ENST00000367651.4	c.555_556insAGCAGCACCCCCGGCGGCTCTGGCAGCAGCTCGGGCGGC	p.Ser173_Gly185dup	inframe_insertion	2/2	1	NM_006079.5	ENSP00000356623	P1
	ENST00000650173.1	n.510-55680_510-55642dup		intron_variant, non_coding_transcript_variant
CITED2	ENST00000536159.2	c.555_556insAGCAGCACCCCCGGCGGCTCTGGCAGCAGCTCGGGCGGC	p.Ser173_Gly185dup	inframe_insertion	2/2	3		ENSP00000442831	P1
CITED2	ENST00000537332.2	c.570_571insAGCAGCACCCCCGGCGGCTCTGGCAGCAGCTCGGGCGGC	p.Ser178_Gly190dup	inframe_insertion	2/2	3		ENSP00000444198

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

CITED2-related disorder Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 24, 2022

The CITED2 c.532_570dup39 variant is predicted to result in an in-frame duplication (p.Ser178_Gly190dup). To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. 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

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-139694526;