NM_002180.3:c.675delT
Variant names:
Variant summary
Our verdict is Pathogenic. Variant got 20 ACMG points: 20P and 0B. PVS1PM2PP3_ModeratePP5_Very_Strong
The NM_002180.3(IGHMBP2):c.675delT(p.Glu226ArgfsTer7) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
IGHMBP2
NM_002180.3 frameshift
NM_002180.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.21
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]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 20 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP3
Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
PP5
Variant 11-68911565-GT-G is Pathogenic according to our data. Variant chr11-68911565-GT-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 9116.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-68911565-GT-G is described in Lovd as [Pathogenic].
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| IGHMBP2 | NM_002180.3 | c.675delT | p.Glu226ArgfsTer7 | frameshift_variant | Exon 5 of 15 | ENST00000255078.8 | NP_002171.2 | |
| IGHMBP2 | XM_047426881.1 | c.675delT | p.Glu226ArgfsTer7 | frameshift_variant | Exon 5 of 15 | XP_047282837.1 | ||
| IGHMBP2 | XM_017017671.3 | c.675delT | p.Glu226ArgfsTer7 | frameshift_variant | Exon 5 of 12 | XP_016873160.1 | ||
| IGHMBP2 | XM_005273976.3 | c.675delT | p.Glu226ArgfsTer7 | frameshift_variant | Exon 5 of 9 | XP_005274033.1 |
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461884Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0AN XY: 727240
GnomAD4 exome
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1461884
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34
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727240
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GnomAD4 genome
GnomAD4 genome
Cov.:
33
ClinVar
Significance: Pathogenic/Likely pathogenic
Submissions summary: Pathogenic:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Autosomal recessive distal spinal muscular atrophy 1 Pathogenic:1
Sep 01, 2001
OMIM
Significance: Pathogenic
Review Status: no assertion criteria provided
Collection Method: literature only
- -
not provided Pathogenic:1
Mar 01, 2020
CeGaT Center for Human Genetics Tuebingen
Significance: Pathogenic
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Charcot-Marie-Tooth disease axonal type 2S Pathogenic:1
Dec 02, 2021
MGZ Medical Genetics Center
Significance: Likely pathogenic
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DG_spliceai
Position offset: -1
Find out detailed SpliceAI scores and Pangolin per-transcript scores at