Genetic Variant TM2D2:c.-247G>A (chr8-38995750-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000397070.6(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
ENST00000397070.6 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.778

Publications

8 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:

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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=-0.69).

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 rank	MANE	Protein	UniProt
TM2D2	NM_078473.3 link	c.228-345G>A		intron_variant	Intron 1 of 3	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.228-345G>A		intron_variant	Intron 1 of 3	1	NM_078473.3	ENSP00000416050.2		Q9BX73-1

Frequencies

GnomAD3 genomes

AF:

0.408

AC:

62044

AN:

151904

Hom.:

13300

Cov.:

show subpopulations

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.:

AF XY:

0.404

AC XY:

213967

AN XY:

529606

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

12289

24578

36867

49156

61445

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13364

26728

40092

53456

66820

<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:

0.408

AC:

62094

AN:

152022

Hom.:

13315

Cov.:

AF XY:

0.415

AC XY:

30834

AN XY:

74294

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1898

3797

5695

7594

9492

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

578

1156

1734

2312

2890

<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:

0.384

Hom.:

3513

Bravo

AF:

0.413

Asia WGS

AF:

0.503

AC:

1750

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

3.4

(source)

DANN

Benign

0.86

PhyloP100

-0.78

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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