rs10105311

Positions:

• chr8-38996522-C-T

Variant summary

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

The ENST00000522142.1(TM2D2):​c.-292+71G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 1,562,718 control chromosomes in the GnomAD database, including 101,405 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 0.31 (7361 hom., cov: 32)
  • Exomes 𝑓: 0.36 (94044 hom.)
• Consequence: TM2D2 ENST00000522142.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.589

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 (NFE) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TM2D2	NM_078473.3			upstream_gene_variant		ENST00000456397.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TM2D2	ENST00000456397.7			upstream_gene_variant		1	NM_078473.3	P1

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46397 AN: 152044 Hom.: 7366 Cov.: 32

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.365

Gnomad AMR AF: 0.313

Gnomad ASJ AF: 0.315

Gnomad EAS AF: 0.203

Gnomad SAS AF: 0.336

Gnomad FIN AF: 0.356

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.361

Gnomad OTH AF: 0.297

GnomAD4 exome AF: 0.363 AC: 512167 AN: 1410554 Hom.: 94044 Cov.: 38 AF XY: 0.363 AC XY: 252258 AN XY: 695324

Gnomad4 AFR exome AF: 0.194

Gnomad4 AMR exome AF: 0.345

Gnomad4 ASJ exome AF: 0.324

Gnomad4 EAS exome AF: 0.226

Gnomad4 SAS exome AF: 0.349

Gnomad4 FIN exome AF: 0.360

Gnomad4 NFE exome AF: 0.377

Gnomad4 OTH exome AF: 0.347

GnomAD4 genome AF: 0.305 AC: 46413 AN: 152164 Hom.: 7361 Cov.: 32 AF XY: 0.304 AC XY: 22638 AN XY: 74378

Gnomad4 AFR AF: 0.205

Gnomad4 AMR AF: 0.312

Gnomad4 ASJ AF: 0.315

Gnomad4 EAS AF: 0.203

Gnomad4 SAS AF: 0.337

Gnomad4 FIN AF: 0.356

Gnomad4 NFE AF: 0.361

Gnomad4 OTH AF: 0.298

Alfa AF: 0.348 Hom.: 12536

Bravo AF: 0.296

Asia WGS AF: 0.275 AC: 955 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	12
DANN	Benign	0.86

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs10105311; hg19: chr8-38854041;