chr4-153315825-C-G

Variant names:

• chr4-153315825-C-G
• rs201299149
• NM_015271.5:c.1615-7C>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_015271.5(TRIM2):​c.1615-7C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000031 in 1,614,064 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000030 (0 hom.)
• Consequence: TRIM2 NM_015271.5 splice_region, intron
• Scores: Splicing: ADA: 0.0002045
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.137
• Publications: 0 publications found

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)

ENSG00000288637 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 4-153315825-C-G is Benign according to our data. Variant chr4-153315825-C-G is described in CliVar as Likely_benign. Clinvar id is 541521.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-153315825-C-G is described in CliVar as Likely_benign. Clinvar id is 541521.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-153315825-C-G is described in CliVar as Likely_benign. Clinvar id is 541521.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-153315825-C-G is described in CliVar as Likely_benign. Clinvar id is 541521.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-153315825-C-G is described in CliVar as Likely_benign. Clinvar id is 541521.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-153315825-C-G is described in CliVar as Likely_benign. Clinvar id is 541521.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-153315825-C-G is described in CliVar as Likely_benign. Clinvar id is 541521.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-153315825-C-G is described in CliVar as Likely_benign. Clinvar id is 541521.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-153315825-C-G is described in CliVar as Likely_benign. Clinvar id is 541521.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-153315825-C-G is described in CliVar as Likely_benign. Clinvar id is 541521.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-153315825-C-G is described in CliVar as Likely_benign. Clinvar id is 541521.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-153315825-C-G is described in CliVar as Likely_benign. Clinvar id is 541521.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-153315825-C-G is described in CliVar as Likely_benign. Clinvar id is 541521.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-153315825-C-G is described in CliVar as Likely_benign. Clinvar id is 541521.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-153315825-C-G is described in CliVar as Likely_benign. Clinvar id is 541521.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-153315825-C-G is described in CliVar as Likely_benign. Clinvar id is 541521.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-153315825-C-G is described in CliVar as Likely_benign. Clinvar id is 541521.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-153315825-C-G is described in CliVar as Likely_benign. Clinvar id is 541521.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-153315825-C-G is described in CliVar as Likely_benign. Clinvar id is 541521.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-153315825-C-G is described in CliVar as Likely_benign. Clinvar id is 541521.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-153315825-C-G is described in CliVar as Likely_benign. Clinvar id is 541521.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-153315825-C-G is described in CliVar as Likely_benign. Clinvar id is 541521.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-153315825-C-G is described in CliVar as Likely_benign. Clinvar id is 541521.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-153315825-C-G is described in CliVar as Likely_benign. Clinvar id is 541521.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-153315825-C-G is described in CliVar as Likely_benign. Clinvar id is 541521.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-153315825-C-G is described in CliVar as Likely_benign. Clinvar id is 541521.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-153315825-C-G is described in CliVar as Likely_benign. Clinvar id is 541521.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-153315825-C-G is described in CliVar as Likely_benign. Clinvar id is 541521.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-153315825-C-G is described in CliVar as Likely_benign. Clinvar id is 541521.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-153315825-C-G is described in CliVar as Likely_benign. Clinvar id is 541521.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-153315825-C-G is described in CliVar as Likely_benign. Clinvar id is 541521.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-153315825-C-G is described in CliVar as Likely_benign. Clinvar id is 541521.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-153315825-C-G is described in CliVar as Likely_benign. Clinvar id is 541521.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-153315825-C-G is described in CliVar as Likely_benign. Clinvar id is 541521.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-153315825-C-G is described in CliVar as Likely_benign. Clinvar id is 541521.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-153315825-C-G is described in CliVar as Likely_benign. Clinvar id is 541521.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-153315825-C-G is described in CliVar as Likely_benign. Clinvar id is 541521.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-153315825-C-G is described in CliVar as Likely_benign. Clinvar id is 541521.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-153315825-C-G is described in CliVar as Likely_benign. Clinvar id is 541521.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-153315825-C-G is described in CliVar as Likely_benign. Clinvar id is 541521.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-153315825-C-G is described in CliVar as Likely_benign. Clinvar id is 541521.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-153315825-C-G is described in CliVar as Likely_benign. Clinvar id is 541521.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-153315825-C-G is described in CliVar as Likely_benign. Clinvar id is 541521.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-153315825-C-G is described in CliVar as Likely_benign. Clinvar id is 541521.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-153315825-C-G is described in CliVar as Likely_benign. Clinvar id is 541521.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-153315825-C-G is described in CliVar as Likely_benign. Clinvar id is 541521.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-153315825-C-G is described in CliVar as Likely_benign. Clinvar id is 541521.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-153315825-C-G is described in CliVar as Likely_benign. Clinvar id is 541521.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-153315825-C-G is described in CliVar as Likely_benign. Clinvar id is 541521.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-153315825-C-G is described in CliVar as Likely_benign. Clinvar id is 541521.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-153315825-C-G is described in CliVar as Likely_benign. Clinvar id is 541521.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-153315825-C-G is described in CliVar as Likely_benign. Clinvar id is 541521.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-153315825-C-G is described in CliVar as Likely_benign. Clinvar id is 541521.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-153315825-C-G is described in CliVar as Likely_benign. Clinvar id is 541521.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-153315825-C-G is described in CliVar as Likely_benign. Clinvar id is 541521.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-153315825-C-G is described in CliVar as Likely_benign. Clinvar id is 541521.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-153315825-C-G is described in CliVar as Likely_benign. Clinvar id is 541521.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-153315825-C-G is described in CliVar as Likely_benign. Clinvar id is 541521.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-153315825-C-G is described in CliVar as Likely_benign. Clinvar id is 541521.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-153315825-C-G is described in CliVar as Likely_benign. Clinvar id is 541521.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-153315825-C-G is described in CliVar as Likely_benign. Clinvar id is 541521.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-153315825-C-G is described in CliVar as Likely_benign. Clinvar id is 541521.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-153315825-C-G is described in CliVar as Likely_benign. Clinvar id is 541521.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-153315825-C-G is described in CliVar as Likely_benign. Clinvar id is 541521.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-153315825-C-G is described in CliVar as Likely_benign. Clinvar id is 541521.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-153315825-C-G is described in CliVar as Likely_benign. Clinvar id is 541521.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-153315825-C-G is described in CliVar as Likely_benign. Clinvar id is 541521.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-153315825-C-G is described in CliVar as Likely_benign. Clinvar id is 541521.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-153315825-C-G is described in CliVar as Likely_benign. Clinvar id is 541521.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-153315825-C-G is described in CliVar as Likely_benign. Clinvar id is 541521.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-153315825-C-G is described in CliVar as Likely_benign. Clinvar id is 541521.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-153315825-C-G is described in CliVar as Likely_benign. Clinvar id is 541521.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-153315825-C-G is described in CliVar as Likely_benign. Clinvar id is 541521.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-153315825-C-G is described in CliVar as Likely_benign. Clinvar id is 541521.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-153315825-C-G is described in CliVar as Likely_benign. Clinvar id is 541521.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-153315825-C-G is described in CliVar as Likely_benign. Clinvar id is 541521.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-153315825-C-G is described in CliVar as Likely_benign. Clinvar id is 541521.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-153315825-C-G is described in CliVar as Likely_benign. Clinvar id is 541521.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-153315825-C-G is described in CliVar as Likely_benign. Clinvar id is 541521.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-153315825-C-G is described in CliVar as Likely_benign. Clinvar id is 541521.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-153315825-C-G is described in CliVar as Likely_benign. Clinvar id is 541521.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-153315825-C-G is described in CliVar as Likely_benign. Clinvar id is 541521.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-153315825-C-G is described in CliVar as Likely_benign. Clinvar id is 541521.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-153315825-C-G is described in CliVar as Likely_benign. Clinvar id is 541521.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-153315825-C-G is described in CliVar as Likely_benign. Clinvar id is 541521.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIM2	NM_015271.5	c.1615-7C>G		splice_region_variant, intron_variant	Intron 7 of 11	ENST00000338700.10	NP_056086.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIM2	ENST00000338700.10	c.1615-7C>G		splice_region_variant, intron_variant	Intron 7 of 11	1	NM_015271.5	ENSP00000339659.5
ENSG00000288637	ENST00000675838.1	c.1534-7C>G		splice_region_variant, intron_variant	Intron 7 of 17			ENSP00000501593.1

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152132 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000955 AC: 24 AN: 251206 AF XY: 0.0000957

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00103

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.0000301 AC: 44 AN: 1461814 Hom.: 0 Cov.: 31 AF XY: 0.0000316 AC XY: 23 AN XY: 727208

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.0000224 AC: 1 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.000554 AC: 22 AN: 39688

South Asian (SAS) AF: 0.0000812 AC: 7 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111986

Other (OTH) AF: 0.000182 AC: 11 AN: 60394

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152250 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74438

African (AFR) AF: 0.00 AC: 0 AN: 41560

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10586

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000340

Asia WGS AF: 0.00520 AC: 18 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Charcot-Marie-Tooth disease type 2R Benign:1

May 21, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely 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	-0.85
CADD	Benign	1.1
DANN	Benign	0.50
PhyloP100		-0.14

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00020
dbscSNV1_RF	Benign	0.046
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

Other links and lift over

dbSNP: rs201299149; hg19: chr4-154236977;