rs10497721

Positions:

• chr2-192049636-C-A
• chr2-192049636-C-G
• chr2-192049636-C-T

Variant summary

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

The NM_016192.4(TMEFF2):​c.536+8043G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0961 in 151,904 control chromosomes in the GnomAD database, including 936 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 0.096 (936 hom., cov: 32)
• Consequence: TMEFF2 NM_016192.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.96

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.298 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEFF2	NM_016192.4	c.536+8043G>T		intron_variant		ENST00000272771.10
CAVIN2-AS1	XR_923723.3	n.8230C>A		non_coding_transcript_exon_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEFF2	ENST00000272771.10	c.536+8043G>T		intron_variant		1	NM_016192.4	P1
TMEFF2	ENST00000392314.5	c.536+8043G>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.0960 AC: 14579 AN: 151786 Hom.: 932 Cov.: 32

Gnomad AFR AF: 0.0444

Gnomad AMI AF: 0.201

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.0503

Gnomad EAS AF: 0.311

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.140

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0985

Gnomad OTH AF: 0.0856

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

GnomAD4 genome AF: 0.0961 AC: 14598 AN: 151904 Hom.: 936 Cov.: 32 AF XY: 0.101 AC XY: 7475 AN XY: 74214

Gnomad4 AFR AF: 0.0443

Gnomad4 AMR AF: 0.106

Gnomad4 ASJ AF: 0.0503

Gnomad4 EAS AF: 0.311

Gnomad4 SAS AF: 0.170

Gnomad4 FIN AF: 0.140

Gnomad4 NFE AF: 0.0985

Gnomad4 OTH AF: 0.0923

Alfa AF: 0.0960 Hom.: 1094

Bravo AF: 0.0902

Asia WGS AF: 0.218 AC: 756 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.13
DANN	Benign	0.36

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: rs10497721; hg19: chr2-192914362;