rs10497726

Positions:

• chr2-192186594-C-A
• chr2-192186594-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000272771.10(TMEFF2):​c.283-2111G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 151,878 control chromosomes in the GnomAD database, including 4,495 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 0.24 (4495 hom., cov: 31)
• Consequence: TMEFF2 ENST00000272771.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.218

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.346 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEFF2	NM_016192.4	c.283-2111G>T		intron_variant		ENST00000272771.10	NP_057276.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEFF2	ENST00000272771.10	c.283-2111G>T		intron_variant		1	NM_016192.4	ENSP00000272771	P1
TMEFF2	ENST00000392314.5	c.283-2111G>T		intron_variant		1		ENSP00000376128
TMEFF2	ENST00000409056.3	c.283-2111G>T		intron_variant		1		ENSP00000386871

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36246 AN: 151760 Hom.: 4496 Cov.: 31

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.360

Gnomad SAS AF: 0.309

Gnomad FIN AF: 0.150

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.265

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

GnomAD4 genome AF: 0.239 AC: 36274 AN: 151878 Hom.: 4495 Cov.: 31 AF XY: 0.238 AC XY: 17671 AN XY: 74234

Gnomad4 AFR AF: 0.216

Gnomad4 AMR AF: 0.277

Gnomad4 ASJ AF: 0.269

Gnomad4 EAS AF: 0.360

Gnomad4 SAS AF: 0.309

Gnomad4 FIN AF: 0.150

Gnomad4 NFE AF: 0.242

Gnomad4 OTH AF: 0.267

Alfa AF: 0.240 Hom.: 6459

Bravo AF: 0.248

Asia WGS AF: 0.280 AC: 972 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.6
DANN	Benign	0.74

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: rs10497726; hg19: chr2-193051320;