8-38995750-C-T

Variant names:

• chr8-38995750-C-T
• rs7006414
• ENST00000397070.6:c.-247G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_031940.4(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 NM_031940.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.778
• Publications: 8 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=-0.69).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.724 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031940.4. 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.228-345G>A		intron	N/A	NP_510882.1	Q9BX73-1
	TM2D2	NM_001024380.2		c.-247G>A		5_prime_UTR	Exon 2 of 4	NP_001019551.1	Q9BX73-2
	TM2D2	NM_031940.4		c.-247G>A		5_prime_UTR	Exon 2 of 4	NP_114146.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TM2D2	ENST00000397070.6	TSL:1	c.-247G>A		5_prime_UTR	Exon 2 of 4	ENSP00000380260.2	Q9BX73-2
	TM2D2	ENST00000456397.7	TSL:1 MANE Select	c.228-345G>A		intron	N/A	ENSP00000416050.2	Q9BX73-1
	TM2D2	ENST00000456845.6	TSL:1	c.-190-57G>A		intron	N/A	ENSP00000391674.2	Q9BX73-2

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

African (AFR) AF: 0.304 AC: 6909 AN: 22696

American (AMR) AF: 0.524 AC: 5645 AN: 10774

Ashkenazi Jewish (ASJ) AF: 0.420 AC: 6099 AN: 14520

East Asian (EAS) AF: 0.706 AC: 16779 AN: 23762

South Asian (SAS) AF: 0.315 AC: 11013 AN: 34998

European-Finnish (FIN) AF: 0.455 AC: 9185 AN: 20208

Middle Eastern (MID) AF: 0.418 AC: 1261 AN: 3014

European-Non Finnish (NFE) AF: 0.401 AC: 376377 AN: 938264

Other (OTH) AF: 0.415 AC: 18677 AN: 45024

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

African (AFR) AF: 0.309 AC: 12830 AN: 41464

American (AMR) AF: 0.506 AC: 7744 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.428 AC: 1486 AN: 3470

East Asian (EAS) AF: 0.743 AC: 3847 AN: 5176

South Asian (SAS) AF: 0.353 AC: 1701 AN: 4818

European-Finnish (FIN) AF: 0.477 AC: 5030 AN: 10546

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.411 AC: 27928 AN: 67946

Other (OTH) AF: 0.425 AC: 896 AN: 2106

Alfa AF: 0.384 Hom.: 3513

Bravo AF: 0.413

Asia WGS AF: 0.503 AC: 1750 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	3.4
DANN	Benign	0.86
PhyloP100		-0.78
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7006414; hg19: chr8-38853269; COSMIC: COSV65959784; COSMIC: COSV65959784;