20-36591351-ATG-CTC

Variant names:

• chr20-36591351-ATG-CTC
• NM_021809.7:c.634_636delATGinsCTC
• TGIF2 p.Met212Leu

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_021809.7(TGIF2):​c.634_636delATGinsCTC​(p.Met212Leu) variant causes a missense change. 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 MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M212V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TGIF2 NM_021809.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.46
• Publications: 0 publications found

Genes affected

TGIF2 (HGNC:15764): (TGFB induced factor homeobox 2) The protein encoded by this gene is a DNA-binding homeobox protein and a transcriptional repressor, which appears to repress transcription by recruiting histone deacetylases to TGF beta-responsive genes. This gene is amplified and over-expressed in some ovarian cancers. Alternative splicing results in multiple transcript variants. A related pseudogene has been identified on chromosome 1. Read-through transcription also exists between this gene and the neighboring downstream C20orf24 (chromosome 20 open reading frame 24) gene. [provided by RefSeq, Dec 2010]

TGIF2-RAB5IF (HGNC:44664): (TGIF2-RAB5IF readthrough) This locus represents naturally occurring read-through transcription between the neighboring TGIF2 (TGFB-induced factor homeobox 2) and C20orf24 (chromosome 20 open reading frame 24) genes. The read-through transcript encodes a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, Dec 2010]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021809.7. 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
	TGIF2	NM_021809.7	MANE Select	c.634_636delATGinsCTC	p.Met212Leu	missense	N/A	NP_068581.1	Q9GZN2-1
	TGIF2	NM_001199513.2		c.634_636delATGinsCTC	p.Met212Leu	missense	N/A	NP_001186442.1	Q9GZN2-1
	TGIF2	NM_001199514.2		c.634_636delATGinsCTC	p.Met212Leu	missense	N/A	NP_001186443.1	Q9GZN2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGIF2	ENST00000373872.9	TSL:1 MANE Select	c.634_636delATGinsCTC	p.Met212Leu	missense	N/A	ENSP00000362979.3	Q9GZN2-1
	TGIF2-RAB5IF	ENST00000558530.1	TSL:3	c.192+12385_192+12387delATGinsCTC		intron	N/A	ENSP00000454021.1
	TGIF2	ENST00000373874.6	TSL:2	c.634_636delATGinsCTC	p.Met212Leu	missense	N/A	ENSP00000362981.2	Q9GZN2-1

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

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.5

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: chr20-35219754;