rs7840270

chr8-38996464-C-Achr8-38996464-C-G

Variant summary

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

The NM_078473.3(TM2D2):c.-25G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.405 in 1,612,466 control chromosomes in the GnomAD database, including 137,129 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 0.38 (12085 hom., cov: 32)
  • Exomes 𝑓: 0.41 (125044 hom.)
• Consequence: TM2D2 NM_078473.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.906

Genes affected

TM2D2 (HGNC:24127): (TM2 domain containing 2) The protein encoded by this gene contains a structural module related to that of the seven transmembrane domain G protein-coupled receptor superfamily. This protein has sequence and structural similarities to the beta-amyloid binding protein (BBP), but, unlike BBP, it does not regulate a response to beta-amyloid peptide. This protein may have regulatory roles in cell death or proliferation signal cascades. This gene has multiple alternatively spliced transcript variants which encode two different isoforms. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.726 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TM2D2	NM_078473.3	c.-25G>T		5_prime_UTR_variant	1/4	ENST00000456397.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TM2D2	ENST00000456397.7	c.-25G>T		5_prime_UTR_variant	1/4	1	NM_078473.3	P1

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57526 AN: 152018 Hom.: 12075 Cov.: 32

Gnomad AFR AF: 0.210

Gnomad AMI AF: 0.525

Gnomad AMR AF: 0.494

Gnomad ASJ AF: 0.427

Gnomad EAS AF: 0.746

Gnomad SAS AF: 0.351

Gnomad FIN AF: 0.476

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.402

GnomAD3 exomes AF: 0.434 AC: 108234 AN: 249286 Hom.: 25322 AF XY: 0.428 AC XY: 57790 AN XY: 134942

Gnomad AFR exome AF: 0.208

Gnomad AMR exome AF: 0.526

Gnomad ASJ exome AF: 0.433

Gnomad EAS exome AF: 0.759

Gnomad SAS exome AF: 0.325

Gnomad FIN exome AF: 0.468

Gnomad NFE exome AF: 0.409

Gnomad OTH exome AF: 0.439

GnomAD4 exome AF: 0.408 AC: 595142 AN: 1460330 Hom.: 125044 Cov.: 54 AF XY: 0.405 AC XY: 293868 AN XY: 726262

Gnomad4 AFR exome AF: 0.208

Gnomad4 AMR exome AF: 0.524

Gnomad4 ASJ exome AF: 0.427

Gnomad4 EAS exome AF: 0.720

Gnomad4 SAS exome AF: 0.325

Gnomad4 FIN exome AF: 0.462

Gnomad4 NFE exome AF: 0.401

Gnomad4 OTH exome AF: 0.412

GnomAD4 genome AF: 0.378 AC: 57565 AN: 152136 Hom.: 12085 Cov.: 32 AF XY: 0.386 AC XY: 28723 AN XY: 74374

Gnomad4 AFR AF: 0.210

Gnomad4 AMR AF: 0.495

Gnomad4 ASJ AF: 0.427

Gnomad4 EAS AF: 0.745

Gnomad4 SAS AF: 0.353

Gnomad4 FIN AF: 0.476

Gnomad4 NFE AF: 0.408

Gnomad4 OTH AF: 0.403

Alfa AF: 0.404 Hom.: 12625

Bravo AF: 0.378

Asia WGS AF: 0.499 AC: 1736 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
Cadd	Benign	10
Dann	Benign	0.44
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs7840270; hg19: chr8-38853983; COSMIC: COSV65959451; COSMIC: COSV65959451;