rs6991968

chr8-38996101-G-Achr8-38996101-G-Cchr8-38996101-G-T

Variant summary

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

The NM_078473.3(TM2D2):c.227+112C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.417 in 1,288,446 control chromosomes in the GnomAD database, including 115,074 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 0.44 (15084 hom., cov: 32)
  • Exomes 𝑓: 0.41 (99990 hom.)
• Consequence: TM2D2 NM_078473.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.205

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=-0.86).
• 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.227+112C>T		intron_variant		ENST00000456397.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TM2D2	ENST00000456397.7	c.227+112C>T		intron_variant		1	NM_078473.3	P1

Frequencies

GnomAD3 genomes AF: 0.444 AC: 66797 AN: 150452 Hom.: 15064 Cov.: 32

Gnomad AFR AF: 0.437

Gnomad AMI AF: 0.524

Gnomad AMR AF: 0.520

Gnomad ASJ AF: 0.428

Gnomad EAS AF: 0.744

Gnomad SAS AF: 0.352

Gnomad FIN AF: 0.475

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.409

Gnomad OTH AF: 0.455

GnomAD4 exome AF: 0.413 AC: 470507 AN: 1137868 Hom.: 99990 AF XY: 0.410 AC XY: 229236 AN XY: 558544

Gnomad4 AFR exome AF: 0.427

Gnomad4 AMR exome AF: 0.531

Gnomad4 ASJ exome AF: 0.424

Gnomad4 EAS exome AF: 0.715

Gnomad4 SAS exome AF: 0.323

Gnomad4 FIN exome AF: 0.462

Gnomad4 NFE exome AF: 0.402

Gnomad4 OTH exome AF: 0.423

GnomAD4 genome AF: 0.444 AC: 66861 AN: 150578 Hom.: 15084 Cov.: 32 AF XY: 0.449 AC XY: 33048 AN XY: 73600

Gnomad4 AFR AF: 0.437

Gnomad4 AMR AF: 0.520

Gnomad4 ASJ AF: 0.428

Gnomad4 EAS AF: 0.744

Gnomad4 SAS AF: 0.354

Gnomad4 FIN AF: 0.475

Gnomad4 NFE AF: 0.409

Gnomad4 OTH AF: 0.456

Alfa AF: 0.422 Hom.: 2179

Bravo AF: 0.448

Asia WGS AF: 0.510 AC: 1776 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	3.2
Dann	Benign	0.68

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: rs6991968; hg19: chr8-38853620;