rs12644284

Variant names:

• chr4-153232848-A-G
• rs12644284
• NM_015271.5:c.30+28288A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015271.5(TRIM2):​c.30+28288A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 152,086 control chromosomes in the GnomAD database, including 3,222 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.18 (3222 hom., cov: 32)
• Consequence: TRIM2 NM_015271.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.481
• Publications: 16 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.266 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.30+28288A>G		intron	N/A	NP_056086.2	Q9C040-2
	TRIM2	NM_001375488.1		c.30+28288A>G		intron	N/A	NP_001362417.1
	TRIM2	NM_001375489.1		c.30+28288A>G		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.30+28288A>G		intron	N/A	ENSP00000339659.5	Q9C040-2
	ENSG00000288637	ENST00000675838.1		c.-52+28288A>G		intron	N/A	ENSP00000501593.1	A0A6Q8PF18
	TRIM2	ENST00000437508.7	TSL:1	c.-48-37490A>G		intron	N/A	ENSP00000415812.2	Q9C040-1

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27851 AN: 151968 Hom.: 3221 Cov.: 32

Gnomad AFR AF: 0.0481

Gnomad AMI AF: 0.283

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.222

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.219

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.191

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

GnomAD4 genome AF: 0.183 AC: 27854 AN: 152086 Hom.: 3222 Cov.: 32 AF XY: 0.179 AC XY: 13277 AN XY: 74336

African (AFR) AF: 0.0480 AC: 1994 AN: 41516

American (AMR) AF: 0.172 AC: 2631 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.222 AC: 769 AN: 3468

East Asian (EAS) AF: 0.104 AC: 541 AN: 5180

South Asian (SAS) AF: 0.133 AC: 640 AN: 4810

European-Finnish (FIN) AF: 0.219 AC: 2308 AN: 10556

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.269 AC: 18267 AN: 67964

Other (OTH) AF: 0.191 AC: 403 AN: 2110

Alfa AF: 0.237 Hom.: 13699

Bravo AF: 0.176

Asia WGS AF: 0.122 AC: 425 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.3
DANN	Benign	0.60
PhyloP100		-0.48
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: rs12644284; hg19: chr4-154154000;