rs12612396

Positions:

• chr2-191967055-G-A
• chr2-191967055-G-C
• chr2-191967055-G-T

Variant summary

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

The NM_016192.4(TMEFF2):​c.746-10677C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.781 in 151,698 control chromosomes in the GnomAD database, including 46,347 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 0.78 (46347 hom., cov: 30)
• Consequence: TMEFF2 NM_016192.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0230

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.915 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEFF2	NM_016192.4	c.746-10677C>T		intron_variant		ENST00000272771.10	NP_057276.2
TMEFF2	NM_001305134.2	c.746-10677C>T		intron_variant			NP_001292063.1
TMEFF2	XM_011510890.4	c.719-10677C>T		intron_variant			XP_011509192.1
TMEFF2	XM_017003739.3	c.719-10677C>T		intron_variant			XP_016859228.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEFF2	ENST00000272771.10	c.746-10677C>T		intron_variant		1	NM_016192.4	ENSP00000272771	P1
TMEFF2	ENST00000392314.5	c.746-10677C>T		intron_variant		1		ENSP00000376128
CAVIN2-AS1	ENST00000424116.7	n.239-67639G>A		intron_variant, non_coding_transcript_variant		2
CAVIN2-AS1	ENST00000428980.6	n.499+44011G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.781 AC: 118420 AN: 151582 Hom.: 46308 Cov.: 30

Gnomad AFR AF: 0.786

Gnomad AMI AF: 0.716

Gnomad AMR AF: 0.784

Gnomad ASJ AF: 0.739

Gnomad EAS AF: 0.937

Gnomad SAS AF: 0.843

Gnomad FIN AF: 0.807

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.760

Gnomad OTH AF: 0.790

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

GnomAD4 genome AF: 0.781 AC: 118512 AN: 151698 Hom.: 46347 Cov.: 30 AF XY: 0.786 AC XY: 58313 AN XY: 74160

Gnomad4 AFR AF: 0.786

Gnomad4 AMR AF: 0.784

Gnomad4 ASJ AF: 0.739

Gnomad4 EAS AF: 0.937

Gnomad4 SAS AF: 0.843

Gnomad4 FIN AF: 0.807

Gnomad4 NFE AF: 0.760

Gnomad4 OTH AF: 0.793

Alfa AF: 0.768 Hom.: 11526

Bravo AF: 0.777

Asia WGS AF: 0.868 AC: 2984 AN: 3438

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	8.2
DANN	Benign	0.21

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: rs12612396; hg19: chr2-192831781;