8-38995750-C-T

Position:

• chr8-38995750-C-T

Variant summary

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

The ENST00000397070.6(TM2D2):​c.-247G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 1,265,282 control chromosomes in the GnomAD database, including 106,828 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 (13315 hom., cov: 33)
  • Exomes 𝑓: 0.41 (93513 hom.)
• Consequence: TM2D2 ENST00000397070.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.778

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=-0.69).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.724 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TM2D2	NM_078473.3	c.228-345G>A		intron_variant		ENST00000456397.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TM2D2	ENST00000456397.7	c.228-345G>A		intron_variant		1	NM_078473.3	P1

Frequencies

GnomAD3 genomes AF: 0.408 AC: 62044 AN: 151904 Hom.: 13300 Cov.: 33

Gnomad AFR AF: 0.309

Gnomad AMI AF: 0.526

Gnomad AMR AF: 0.506

Gnomad ASJ AF: 0.428

Gnomad EAS AF: 0.744

Gnomad SAS AF: 0.351

Gnomad FIN AF: 0.477

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.411

Gnomad OTH AF: 0.424

GnomAD4 exome AF: 0.406 AC: 451945 AN: 1113260 Hom.: 93513 Cov.: 31 AF XY: 0.404 AC XY: 213967 AN XY: 529606

Gnomad4 AFR exome AF: 0.304

Gnomad4 AMR exome AF: 0.524

Gnomad4 ASJ exome AF: 0.420

Gnomad4 EAS exome AF: 0.706

Gnomad4 SAS exome AF: 0.315

Gnomad4 FIN exome AF: 0.455

Gnomad4 NFE exome AF: 0.401

Gnomad4 OTH exome AF: 0.415

GnomAD4 genome AF: 0.408 AC: 62094 AN: 152022 Hom.: 13315 Cov.: 33 AF XY: 0.415 AC XY: 30834 AN XY: 74294

Gnomad4 AFR AF: 0.309

Gnomad4 AMR AF: 0.506

Gnomad4 ASJ AF: 0.428

Gnomad4 EAS AF: 0.743

Gnomad4 SAS AF: 0.353

Gnomad4 FIN AF: 0.477

Gnomad4 NFE AF: 0.411

Gnomad4 OTH AF: 0.425

Alfa AF: 0.409 Hom.: 2682

Bravo AF: 0.413

Asia WGS AF: 0.503 AC: 1750 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	3.4
DANN	Benign	0.86

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs7006414; hg19: chr8-38853269; COSMIC: COSV65959784; COSMIC: COSV65959784;