chr2-191956313-C-T

Variant names:

• chr2-191956313-C-T
• rs1342749759
• NM_016192.4:c.811G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016192.4(TMEFF2):​c.811G>A​(p.Gly271Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TMEFF2 NM_016192.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.89
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20513844).

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.811G>A	p.Gly271Ser	missense	Exon 8 of 10	NP_057276.2
	TMEFF2	NM_001305134.2		c.811G>A	p.Gly271Ser	missense	Exon 8 of 10	NP_001292063.1	Q9UIK5-2
	CAVIN2-AS1	NR_187184.1		n.285-78381C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEFF2	ENST00000272771.10	TSL:1 MANE Select	c.811G>A	p.Gly271Ser	missense	Exon 8 of 10	ENSP00000272771.5	Q9UIK5-1
	TMEFF2	ENST00000392314.5	TSL:1	c.811G>A	p.Gly271Ser	missense	Exon 8 of 10	ENSP00000376128.1	Q9UIK5-2
	TMEFF2	ENST00000877060.1		c.853G>A	p.Gly285Ser	missense	Exon 9 of 11	ENSP00000547119.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.095	T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.0028
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.0088	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.47	N
PhyloP100		3.9
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.070
Sift	Benign	0.037	D
Sift4G	Benign	0.30	T
Polyphen		0.059	B
Vest4		0.32
MutPred		0.64		Gain of disorder (P = 0.0971)
MVP		0.53
MPC		0.77
ClinPred		0.82	D
GERP RS		4.5
Varity_R		0.17
gMVP		0.55
Mutation Taster		=84/16	polymorphism

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

Other links and lift over

dbSNP: rs1342749759; hg19: chr2-192821039; COSMIC: COSV55833927;