dbSNP rs7840270: TM2D2:c.-25G>T (chr8-38996464-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.906

Publications

23 publications found

Variant links:

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]

TM2D2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TM2D2	NM_078473.3 link	c.-25G>T		5_prime_UTR_variant	Exon 1 of 4	ENST00000456397.7	NP_510882.1	Q9BX73-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TM2D2	ENST00000456397.7 link	c.-25G>T		5_prime_UTR_variant	Exon 1 of 4	1	NM_078473.3	ENSP00000416050.2		Q9BX73-1

Frequencies

GnomAD3 genomes

AF:

0.378

AC:

57526

AN:

152018

Hom.:

12075

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.405

AC XY:

293868

AN XY:

726262

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

22331

44662

66992

89323

111654

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13876

27752

41628

55504

69380

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.378

AC:

57565

AN:

152136

Hom.:

12085

Cov.:

AF XY:

0.386

AC XY:

28723

AN XY:

74374

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1770

3540

5309

7079

8849

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

544

1088

1632

2176

2720

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

(source)

DANN

Benign

0.44

PhyloP100

0.91

PromoterAI

0.069

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over