Variant rs35333794 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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 links:

ENSG00000288637 (HGNC:):

ENSG00000288637 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 474616.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-153295396-C-T is described in Lovd as [Benign].

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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 18 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM2	NM_015271.5 linkuse as main transcript	c.870C>T	p.Asn290Asn	synonymous_variant	6/12	ENST00000338700.10	NP_056086.2	Q9C040-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM2	ENST00000338700.10 linkuse as main transcript	c.870C>T	p.Asn290Asn	synonymous_variant	6/12	1	NM_015271.5	ENSP00000339659.5		Q9C040-2
ENSG00000288637	ENST00000675079.1 linkuse as main transcript	c.789C>T	p.Asn263Asn	synonymous_variant	6/18			ENSP00000502677.1		A0A6Q8PHG4

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

GnomAD3 exomes

AF:

0.0149

AC:

3735

AN:

250904

Hom.:

AF XY:

0.0144

AC XY:

1954

AN XY:

135630

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 SAS exome

AF:

0.00759

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

Gnomad4 AFR exome

AF:

0.00245

Gnomad4 AMR exome

AF:

0.0363

Gnomad4 ASJ exome

AF:

0.00165

Gnomad4 EAS exome

AF:

0.0130

Gnomad4 SAS exome

AF:

0.00767

Gnomad4 FIN exome

AF:

0.0118

Gnomad4 NFE exome

AF:

0.0189

Gnomad4 OTH exome

AF:

0.0141

GnomAD4 genome

AF:

0.0120

AC:

1830

AN:

152338

Hom.:

Cov.:

AF XY:

0.0116

AC XY:

867

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.00349

Gnomad4 AMR

AF:

0.0176

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00425

Gnomad4 SAS

AF:

0.00641

Gnomad4 FIN

AF:

0.0155

Gnomad4 NFE

AF:

0.0163

Gnomad4 OTH

AF:

0.00946

Alfa

AF:

0.0136

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 20, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Charcot-Marie-Tooth disease type 2R

Benign:2

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Oct 26, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

8.7

DANN

Benign

0.91

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over