chr8-38996464-C-A

Variant names:

• chr8-38996464-C-A
• rs7840270
• NM_078473.3:c.-25G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 23 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_078473.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TM2D2	NM_078473.3	MANE Select	c.-25G>T		5_prime_UTR	Exon 1 of 4	NP_510882.1	Q9BX73-1
	TM2D2	NM_001024380.2		c.-337G>T		5_prime_UTR	Exon 1 of 4	NP_001019551.1	Q9BX73-2
	TM2D2	NM_001024381.2		c.-236G>T		5_prime_UTR	Exon 1 of 4	NP_001019552.1	Q9BX73-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TM2D2	ENST00000456397.7	TSL:1 MANE Select	c.-25G>T		5_prime_UTR	Exon 1 of 4	ENSP00000416050.2	Q9BX73-1
	TM2D2	ENST00000397070.6	TSL:1	c.-543G>T		5_prime_UTR	Exon 1 of 4	ENSP00000380260.2	Q9BX73-2
	TM2D2	ENST00000456845.6	TSL:1	c.-236G>T		5_prime_UTR	Exon 1 of 4	ENSP00000391674.2	Q9BX73-2

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

GnomAD2 exomes AF: 0.434 AC: 108234 AN: 249286 AF XY: 0.428

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 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

African (AFR) AF: 0.208 AC: 6961 AN: 33466

American (AMR) AF: 0.524 AC: 23394 AN: 44628

Ashkenazi Jewish (ASJ) AF: 0.427 AC: 11152 AN: 26118

East Asian (EAS) AF: 0.720 AC: 28554 AN: 39666

South Asian (SAS) AF: 0.325 AC: 28001 AN: 86202

European-Finnish (FIN) AF: 0.462 AC: 24490 AN: 53006

Middle Eastern (MID) AF: 0.418 AC: 2404 AN: 5758

European-Non Finnish (NFE) AF: 0.401 AC: 445313 AN: 1111152

Other (OTH) AF: 0.412 AC: 24873 AN: 60334

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

African (AFR) AF: 0.210 AC: 8721 AN: 41524

American (AMR) AF: 0.495 AC: 7560 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.427 AC: 1480 AN: 3468

East Asian (EAS) AF: 0.745 AC: 3843 AN: 5156

South Asian (SAS) AF: 0.353 AC: 1704 AN: 4824

European-Finnish (FIN) AF: 0.476 AC: 5041 AN: 10592

Middle Eastern (MID) AF: 0.521 AC: 152 AN: 292

European-Non Finnish (NFE) AF: 0.408 AC: 27733 AN: 67966

Other (OTH) AF: 0.403 AC: 852 AN: 2114

Alfa AF: 0.398 Hom.: 16167

Bravo AF: 0.378

Asia WGS AF: 0.499 AC: 1736 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	10
DANN	Benign	0.44
PhyloP100		0.91
PromoterAI		0.069	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7840270; hg19: chr8-38853983; COSMIC: COSV65959451; COSMIC: COSV65959451;