2-192065634-A-G

Variant names:

• chr2-192065634-A-G
• rs2884026
• NM_016192.4:c.440-7859T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016192.4(TMEFF2):​c.440-7859T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.409 in 151,360 control chromosomes in the GnomAD database, including 14,529 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.41 (14529 hom., cov: 31)
• Consequence: TMEFF2 NM_016192.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.590
• Publications: 3 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.527 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEFF2	NM_016192.4	c.440-7859T>C		intron_variant	Intron 4 of 9	ENST00000272771.10	NP_057276.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEFF2	ENST00000272771.10	c.440-7859T>C		intron_variant	Intron 4 of 9	1	NM_016192.4	ENSP00000272771.5
TMEFF2	ENST00000392314.5	c.440-7859T>C		intron_variant	Intron 4 of 9	1		ENSP00000376128.1
CAVIN2-AS1	ENST00000792812.1	n.598+7826A>G		intron_variant	Intron 3 of 4

Frequencies

GnomAD3 genomes AF: 0.410 AC: 61935 AN: 151244 Hom.: 14526 Cov.: 31

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.581

Gnomad AMR AF: 0.511

Gnomad ASJ AF: 0.494

Gnomad EAS AF: 0.530

Gnomad SAS AF: 0.542

Gnomad FIN AF: 0.541

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.493

Gnomad OTH AF: 0.437

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.409 AC: 61937 AN: 151360 Hom.: 14529 Cov.: 31 AF XY: 0.418 AC XY: 30893 AN XY: 73924

African (AFR) AF: 0.159 AC: 6584 AN: 41400

American (AMR) AF: 0.511 AC: 7739 AN: 15152

Ashkenazi Jewish (ASJ) AF: 0.494 AC: 1709 AN: 3458

East Asian (EAS) AF: 0.529 AC: 2714 AN: 5128

South Asian (SAS) AF: 0.545 AC: 2618 AN: 4806

European-Finnish (FIN) AF: 0.541 AC: 5694 AN: 10516

Middle Eastern (MID) AF: 0.483 AC: 138 AN: 286

European-Non Finnish (NFE) AF: 0.493 AC: 33293 AN: 67598

Other (OTH) AF: 0.436 AC: 919 AN: 2106

Alfa AF: 0.441 Hom.: 2714

Bravo AF: 0.397

Asia WGS AF: 0.519 AC: 1794 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.92
DANN	Benign	0.78
PhyloP100		-0.59
Mutation Taster		=100/0	polymorphism (auto)

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: rs2884026; hg19: chr2-192930360;