6-139373260-TAAG-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PM4_Supporting

The NM_006079.5(CITED2):​c.682_684del​(p.Leu228del) variant causes a inframe deletion change involving the alteration of a 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_deletion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.86
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 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in NM_006079.5. Strenght limited to Supporting due to length of the change: 1aa.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CITED2NM_006079.5 linkuse as main transcriptc.682_684del p.Leu228del inframe_deletion 2/2 ENST00000367651.4 NP_006070.2
CITED2NM_001168388.3 linkuse as main transcriptc.682_684del p.Leu228del inframe_deletion 2/2 NP_001161860.1
CITED2NM_001168389.3 linkuse as main transcriptc.697_699del p.Leu233del inframe_deletion 2/2 NP_001161861.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CITED2ENST00000367651.4 linkuse as main transcriptc.682_684del p.Leu228del inframe_deletion 2/21 NM_006079.5 ENSP00000356623 P1Q99967-1
ENST00000650173.1 linkuse as main transcriptn.510-55818_510-55816del intron_variant, non_coding_transcript_variant
CITED2ENST00000536159.2 linkuse as main transcriptc.682_684del p.Leu228del inframe_deletion 2/23 ENSP00000442831 P1Q99967-1
CITED2ENST00000537332.2 linkuse as main transcriptc.697_699del p.Leu233del inframe_deletion 2/23 ENSP00000444198

Frequencies

GnomAD3 genomes
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingGeneDxOct 17, 2019Not observed in large population cohorts (Lek et al., 2016); In-frame deletion of 1 amino acid in a non-repeat region; In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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: chr6-139694397; API