2-191953738-TGC-GGT

Variant names:

• chr2-191953738-TGC-GGT
• NM_016192.4:c.967_969delGCAinsACC
• TMEFF2 p.Ala323Thr

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_016192.4(TMEFF2):​c.967_969delGCAinsACC​(p.Ala323Thr) variant causes a missense change involving the alteration of a conserved nucleotide. 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TMEFF2 NM_016192.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.54
• Publications: 0 publications found

Genes affected

TMEFF2 (HGNC:11867): (transmembrane protein with EGF like and two follistatin like domains 2) This gene encodes a member of the tomoregulin family of transmembrane proteins. This protein has been shown to function as both an oncogene and a tumor suppressor depending on the cellular context and may regulate prostate cancer cell invasion. Multiple soluble forms of this protein have been identified that arise from both an alternative splice variant and ectodomain shedding. Additionally, this gene has been found to be hypermethylated in multiple cancer types. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2015]

CAVIN2-AS1 (HGNC:40517): (CAVIN2 and TMEFF2 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016192.4. 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
	TMEFF2	NM_016192.4	MANE Select	c.967_969delGCAinsACC	p.Ala323Thr	missense	N/A	NP_057276.2
	TMEFF2	NM_001305134.2		c.967_969delGCAinsACC	p.Ala323Thr	missense	N/A	NP_001292063.1	Q9UIK5-2
	CAVIN2-AS1	NR_187184.1		n.285-80956_285-80954delTGCinsGGT		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEFF2	ENST00000272771.10	TSL:1 MANE Select	c.967_969delGCAinsACC	p.Ala323Thr	missense	N/A	ENSP00000272771.5	Q9UIK5-1
	TMEFF2	ENST00000392314.5	TSL:1	c.967_969delGCAinsACC	p.Ala323Thr	missense	N/A	ENSP00000376128.1	Q9UIK5-2
	TMEFF2	ENST00000877060.1		c.1009_1011delGCAinsACC	p.Ala337Thr	missense	N/A	ENSP00000547119.1

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		9.5

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: chr2-192818464;