chr4-153323801-T-C

Variant names:

• chr4-153323801-T-C
• rs10517569
• NM_015271.5:c.1952-277T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_015271.5(TRIM2):​c.1952-277T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 152,192 control chromosomes in the GnomAD database, including 1,594 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.12 (1594 hom., cov: 32)
• Consequence: TRIM2 NM_015271.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0280
• Publications: 5 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 4-153323801-T-C is Benign according to our data. Variant chr4-153323801-T-C is described in ClinVar as Benign. ClinVar VariationId is 1271921.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.269 is higher than 0.05.

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.1952-277T>C		intron	N/A	NP_056086.2	Q9C040-2
	TRIM2	NM_001375488.1		c.2045-277T>C		intron	N/A	NP_001362417.1
	TRIM2	NM_001375489.1		c.2042-277T>C		intron	N/A	NP_001362418.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM2	ENST00000338700.10	TSL:1 MANE Select	c.1952-277T>C		intron	N/A	ENSP00000339659.5	Q9C040-2
	ENSG00000288637	ENST00000675838.1		c.1871-277T>C		intron	N/A	ENSP00000501593.1	A0A6Q8PF18
	TRIM2	ENST00000437508.7	TSL:1	c.1871-277T>C		intron	N/A	ENSP00000415812.2	Q9C040-1

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18790 AN: 152076 Hom.: 1592 Cov.: 32

Gnomad AFR AF: 0.0264

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.0971

Gnomad SAS AF: 0.282

Gnomad FIN AF: 0.238

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.141

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.123 AC: 18782 AN: 152192 Hom.: 1594 Cov.: 32 AF XY: 0.130 AC XY: 9647 AN XY: 74382

African (AFR) AF: 0.0263 AC: 1095 AN: 41568

American (AMR) AF: 0.105 AC: 1609 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 531 AN: 3468

East Asian (EAS) AF: 0.0970 AC: 503 AN: 5188

South Asian (SAS) AF: 0.282 AC: 1353 AN: 4806

European-Finnish (FIN) AF: 0.238 AC: 2512 AN: 10550

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.156 AC: 10593 AN: 68000

Other (OTH) AF: 0.144 AC: 304 AN: 2114

Alfa AF: 0.152 Hom.: 2903

Bravo AF: 0.107

Asia WGS AF: 0.188 AC: 654 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	12
DANN	Benign	0.66
PhyloP100		0.028
Mutation Taster		=100/0	polymorphism (auto)

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: rs10517569; hg19: chr4-154244953;