rs2884026

chr2-192065634-A-Gchr2-192065634-A-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
TMEFF2	NM_016192.4	c.440-7859T>C		intron_variant		ENST00000272771.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEFF2	ENST00000272771.10	c.440-7859T>C		intron_variant		1	NM_016192.4	P1
TMEFF2	ENST00000392314.5	c.440-7859T>C		intron_variant		1

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

Gnomad4 AFR AF: 0.159

Gnomad4 AMR AF: 0.511

Gnomad4 ASJ AF: 0.494

Gnomad4 EAS AF: 0.529

Gnomad4 SAS AF: 0.545

Gnomad4 FIN AF: 0.541

Gnomad4 NFE AF: 0.493

Gnomad4 OTH AF: 0.436

Alfa AF: 0.449 Hom.: 2705

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

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

LitVar

Other links and lift over

dbSNP: rs2884026; hg19: chr2-192930360;