rs149607572

Variant names:

• chr4-153295342-C-T
• rs149607572
• NM_015271.5:c.816C>T

Your query was ambiguous. Multiple possible variants found:

• chr4-153295342-C-T
• chr4-153295342-C-G

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 2P and 13B. PM2 BP4_Strong BP6_Very_Strong BP7

The NM_015271.5(TRIM2):​c.816C>T​(p.Leu272Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000153 in 1,609,924 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00020 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00015 (1 hom.)
• Consequence: TRIM2 NM_015271.5 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.100
• 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet

ENSG00000288637 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 4-153295342-C-T is Benign according to our data. Variant chr4-153295342-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 541519.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.1 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015271.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM2	NM_015271.5	MANE Select	c.816C>T	p.Leu272Leu	synonymous	Exon 6 of 12	NP_056086.2	Q9C040-2
	TRIM2	NM_001375488.1		c.909C>T	p.Leu303Leu	synonymous	Exon 7 of 13	NP_001362417.1
	TRIM2	NM_001375489.1		c.906C>T	p.Leu302Leu	synonymous	Exon 7 of 13	NP_001362418.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM2	ENST00000338700.10	TSL:1 MANE Select	c.816C>T	p.Leu272Leu	synonymous	Exon 6 of 12	ENSP00000339659.5	Q9C040-2
	ENSG00000288637	ENST00000675838.1		c.735C>T	p.Leu245Leu	synonymous	Exon 6 of 18	ENSP00000501593.1	A0A6Q8PF18
	TRIM2	ENST00000437508.7	TSL:1	c.735C>T	p.Leu245Leu	synonymous	Exon 6 of 12	ENSP00000415812.2	Q9C040-1

Frequencies

GnomAD3 genomes AF: 0.000204 AC: 31 AN: 152228 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00864

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000315 AC: 77 AN: 244790 AF XY: 0.000295

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00662

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000634

Gnomad OTH exome AF: 0.000837

GnomAD4 exome AF: 0.000147 AC: 215 AN: 1457696 Hom.: 1 Cov.: 30 AF XY: 0.000163 AC XY: 118 AN XY: 724784

African (AFR) AF: 0.00 AC: 0 AN: 33380

American (AMR) AF: 0.00 AC: 0 AN: 44252

Ashkenazi Jewish (ASJ) AF: 0.00644 AC: 167 AN: 25912

East Asian (EAS) AF: 0.00 AC: 0 AN: 39566

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85472

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53224

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5730

European-Non Finnish (NFE) AF: 0.0000207 AC: 23 AN: 1109948

Other (OTH) AF: 0.000399 AC: 24 AN: 60212

GnomAD4 genome AF: 0.000204 AC: 31 AN: 152228 Hom.: 0 Cov.: 33 AF XY: 0.000202 AC XY: 15 AN XY: 74370

African (AFR) AF: 0.00 AC: 0 AN: 41464

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00864 AC: 30 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000557 Hom.: 2

Bravo AF: 0.000193

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Charcot-Marie-Tooth disease type 2R (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	5.1
DANN	Benign	0.87
PhyloP100		-0.10
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs149607572; hg19: chr4-154216494;