rs35333794

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_015271.5(TRIM2):c.870C>T(p.Asn290Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0169 in 1,614,112 control chromosomes in the GnomAD database, including 318 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 18 hom., cov: 32)

Exomes 𝑓: 0.017 ( 300 hom. )

Consequence

TRIM2
NM_015271.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.21

Publications

6 publications found

Variant links:

Genes affected

TRIM2 (HGNC:15974): (tripartite motif containing 2) The protein encoded by this gene is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. The protein localizes to cytoplasmic filaments. It plays a neuroprotective role and functions as an E3-ubiquitin ligase in proteasome-mediated degradation of target proteins. Mutations in this gene can cause early-onset axonal neuropathy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2014]

TRIM2 Gene-Disease associations (from GenCC):

Charcot-Marie-Tooth disease type 2R
Inheritance: AR Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)

TRIM2 links:

ENSG00000288637 (HGNC:):

ENSG00000288637 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 4-153295396-C-T is Benign according to our data. Variant chr4-153295396-C-T is described in ClinVar as Benign. ClinVar VariationId is 474616.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.21 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.012 (1830/152338) while in subpopulation AMR AF = 0.0176 (269/15312). AF 95% confidence interval is 0.0158. There are 18 homozygotes in GnomAd4. There are 867 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 18 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIM2	NM_015271.5 link	c.870C>T	p.Asn290Asn	synonymous_variant	Exon 6 of 12	ENST00000338700.10	NP_056086.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIM2	ENST00000338700.10 link	c.870C>T	p.Asn290Asn	synonymous_variant	Exon 6 of 12	1	NM_015271.5	ENSP00000339659.5
ENSG00000288637	ENST00000675838.1 link	c.789C>T	p.Asn263Asn	synonymous_variant	Exon 6 of 18			ENSP00000501593.1

Frequencies

GnomAD3 genomes

AF:

0.0120

AC:

1831

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00350

Gnomad AMI

AF:

0.0647

Gnomad AMR

AF:

0.0176

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00424

Gnomad SAS

AF:

0.00641

Gnomad FIN

AF:

0.0155

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0163

Gnomad OTH

AF:

0.00956

GnomAD2 exomes

AF:

0.0149

AC:

3735

AN:

250904

AF XY:

0.0144

show subpopulations

Gnomad AFR exome

AF:

0.00290

Gnomad AMR exome

AF:

0.0378

Gnomad ASJ exome

AF:

0.00189

Gnomad EAS exome

AF:

0.00299

Gnomad FIN exome

AF:

0.0134

Gnomad NFE exome

AF:

0.0151

Gnomad OTH exome

AF:

0.0124

GnomAD4 exome

AF:

0.0174

AC:

25436

AN:

1461774

Hom.:

300

Cov.:

AF XY:

0.0169

AC XY:

12318

AN XY:

727154

show subpopulations

African (AFR)

AF:

0.00245

AC:

AN:

33480

American (AMR)

AF:

0.0363

AC:

1624

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.00165

AC:

AN:

26134

East Asian (EAS)

AF:

0.0130

AC:

517

AN:

39696

South Asian (SAS)

AF:

0.00767

AC:

661

AN:

86232

European-Finnish (FIN)

AF:

0.0118

AC:

632

AN:

53408

Middle Eastern (MID)

AF:

0.00329

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0189

AC:

21005

AN:

1111950

Other (OTH)

AF:

0.0141

AC:

853

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

1576

3152

4727

6303

7879

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

834

1668

2502

3336

4170

<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:

0.0120

AC:

1830

AN:

152338

Hom.:

Cov.:

AF XY:

0.0116

AC XY:

867

AN XY:

74498

show subpopulations

African (AFR)

AF:

0.00349

AC:

145

AN:

41582

American (AMR)

AF:

0.0176

AC:

269

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00173

AC:

AN:

3470

East Asian (EAS)

AF:

0.00425

AC:

AN:

5176

South Asian (SAS)

AF:

0.00641

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.0155

AC:

165

AN:

10628

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0163

AC:

1110

AN:

68016

Other (OTH)

AF:

0.00946

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

179

268

358

447

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.0150

Hom.:

Bravo

AF:

0.0121

Asia WGS

AF:

0.00635

AC:

AN:

3478

EpiCase

AF:

0.0144

EpiControl

AF:

0.0144

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Aug 20, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Charcot-Marie-Tooth disease type 2R

Benign:2

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Nov 04, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

8.7

(source)

DANN

Benign

0.91

PhyloP100

1.2

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over