NM_002180.3:c.-2C>T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002180.3(IGHMBP2):c.-2C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 1,569,878 control chromosomes in the GnomAD database, including 41,782 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 3026 hom., cov: 35)

Exomes 𝑓: 0.23 ( 38756 hom. )

Consequence

IGHMBP2
NM_002180.3 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: 0.0100

Variant links:

Genes affected

IGHMBP2 (HGNC:5542): (immunoglobulin mu DNA binding protein 2) This gene encodes a helicase superfamily member that binds a specific DNA sequence from the immunoglobulin mu chain switch region. Mutations in this gene lead to spinal muscle atrophy with respiratory distress type 1. [provided by RefSeq, Jul 2008]

IGHMBP2 links:

MRPL21 (HGNC:14479): (mitochondrial ribosomal protein L21) Mammalian mitochondrial ribosomal proteins are encoded by nuclear genes and help in protein synthesis within the mitochondrion. Mitochondrial ribosomes (mitoribosomes) consist of a small 28S subunit and a large 39S subunit. They have an estimated 75% protein to rRNA composition compared to prokaryotic ribosomes, where this ratio is reversed. Another difference between mammalian mitoribosomes and prokaryotic ribosomes is that the latter contain a 5S rRNA. Among different species, the proteins comprising the mitoribosome differ greatly in sequence, and sometimes in biochemical properties, which prevents easy recognition by sequence homology. This gene encodes a 39S subunit protein. Multiple transcript variants encoding different isoforms were identified through sequence analysis although some may be subject to nonsense-mediated decay (NMD). [provided by RefSeq, Jul 2008]

MRPL21 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 11-68903951-C-T is Benign according to our data. Variant chr11-68903951-C-T is described in ClinVar as [Benign]. Clinvar id is 258555.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-68903951-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.246 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGHMBP2	NM_002180.3 link	c.-2C>T		5_prime_UTR_variant	Exon 1 of 15	ENST00000255078.8	NP_002171.2	P38935
MRPL21	NM_181514.2 link	c.-141G>A		upstream_gene_variant		ENST00000362034.7	NP_852615.1	Q7Z2W9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGHMBP2	ENST00000255078 link	c.-2C>T		5_prime_UTR_variant	Exon 1 of 15	1	NM_002180.3	ENSP00000255078.4		P38935
MRPL21	ENST00000362034.7 link	c.-141G>A		upstream_gene_variant		1	NM_181514.2	ENSP00000354580.2		Q7Z2W9-1

Frequencies

GnomAD3 genomes

AF:

0.184

AC:

27968

AN:

152008

Hom.:

3023

Cov.:

show subpopulations

Gnomad AFR

AF:

0.103

Gnomad AMI

AF:

0.305

Gnomad AMR

AF:

0.208

Gnomad ASJ

AF:

0.287

Gnomad EAS

AF:

0.0241

Gnomad SAS

AF:

0.0607

Gnomad FIN

AF:

0.124

Gnomad MID

AF:

0.203

Gnomad NFE

AF:

0.250

Gnomad OTH

AF:

0.244

GnomAD3 exomes

AF:

0.187

AC:

33258

AN:

177460

Hom.:

3698

AF XY:

0.186

AC XY:

17875

AN XY:

96106

show subpopulations

Gnomad AFR exome

AF:

0.106

Gnomad AMR exome

AF:

0.191

Gnomad ASJ exome

AF:

0.284

Gnomad EAS exome

AF:

0.0257

Gnomad SAS exome

AF:

0.0713

Gnomad FIN exome

AF:

0.132

Gnomad NFE exome

AF:

0.265

Gnomad OTH exome

AF:

0.225

GnomAD4 exome

AF:

0.225

AC:

319618

AN:

1417752

Hom.:

38756

Cov.:

AF XY:

0.221

AC XY:

155113

AN XY:

701912

show subpopulations

Gnomad4 AFR exome

AF:

0.100

Gnomad4 AMR exome

AF:

0.188

Gnomad4 ASJ exome

AF:

0.283

Gnomad4 EAS exome

AF:

0.0273

Gnomad4 SAS exome

AF:

0.0706

Gnomad4 FIN exome

AF:

0.133

Gnomad4 NFE exome

AF:

0.252

Gnomad4 OTH exome

AF:

0.214

GnomAD4 genome

AF:

0.184

AC:

27984

AN:

152126

Hom.:

3026

Cov.:

AF XY:

0.176

AC XY:

13124

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.103

Gnomad4 AMR

AF:

0.207

Gnomad4 ASJ

AF:

0.287

Gnomad4 EAS

AF:

0.0244

Gnomad4 SAS

AF:

0.0601

Gnomad4 FIN

AF:

0.124

Gnomad4 NFE

AF:

0.250

Gnomad4 OTH

AF:

0.241

Alfa

AF:

0.240

Hom.:

2515

Bravo

AF:

0.190

Asia WGS

AF:

0.0550

AC:

192

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: 25% of total chromosomes in ExAC -

Apr 29, 2016

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 16, 2017

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Autosomal recessive distal spinal muscular atrophy 1

Benign:2

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Charcot-Marie-Tooth disease

Benign:1

Molecular Genetics Laboratory, London Health Sciences Centre

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Charcot-Marie-Tooth disease axonal type 2S

Benign:1

Aug 10, 2021

Genome-Nilou Lab

Significance: 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

-0.53

CADD

Benign

DANN

Uncertain

0.99

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.0

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