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6-139373389-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

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.704
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CITED2NM_006079.5 linkuse as main transcriptc.555_556insAGCAGCACCCCCGGCGGCTCTGGCAGCAGCTCGGGCGGC p.Ser173_Gly185dup inframe_insertion 2/2 ENST00000367651.4
CITED2NM_001168388.3 linkuse as main transcriptc.555_556insAGCAGCACCCCCGGCGGCTCTGGCAGCAGCTCGGGCGGC p.Ser173_Gly185dup inframe_insertion 2/2
CITED2NM_001168389.3 linkuse as main transcriptc.570_571insAGCAGCACCCCCGGCGGCTCTGGCAGCAGCTCGGGCGGC p.Ser178_Gly190dup inframe_insertion 2/2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CITED2ENST00000367651.4 linkuse as main transcriptc.555_556insAGCAGCACCCCCGGCGGCTCTGGCAGCAGCTCGGGCGGC p.Ser173_Gly185dup inframe_insertion 2/21 NM_006079.5 P1Q99967-1
ENST00000650173.1 linkuse as main transcriptn.510-55680_510-55642dup intron_variant, non_coding_transcript_variant
CITED2ENST00000536159.2 linkuse as main transcriptc.555_556insAGCAGCACCCCCGGCGGCTCTGGCAGCAGCTCGGGCGGC p.Ser173_Gly185dup inframe_insertion 2/23 P1Q99967-1
CITED2ENST00000537332.2 linkuse as main transcriptc.570_571insAGCAGCACCCCCGGCGGCTCTGGCAGCAGCTCGGGCGGC p.Ser178_Gly190dup inframe_insertion 2/23

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

CITED2-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesOct 24, 2022The 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

Name
Calibrated prediction
Score
Prediction

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; API