11-68933499-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002180.3(IGHMBP2):c.1418+18A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0189 in 1,603,258 control chromosomes in the GnomAD database, including 1,603 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.060 ( 736 hom., cov: 33)

Exomes 𝑓: 0.015 ( 867 hom. )

Consequence

IGHMBP2
NM_002180.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -4.04

Publications

2 publications found

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 Gene-Disease associations (from GenCC):

autosomal recessive distal spinal muscular atrophy 1
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Ambry Genetics, Genomics England PanelApp, Orphanet, Labcorp Genetics (formerly Invitae)
Charcot-Marie-Tooth disease axonal type 2S
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Laboratory for Molecular Medicine, Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)
hereditary peripheral neuropathy
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen

IGHMBP2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 11-68933499-A-G is Benign according to our data. Variant chr11-68933499-A-G is described in ClinVar as Benign. ClinVar VariationId is 258556.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGHMBP2	NM_002180.3 link	c.1418+18A>G		intron_variant	Intron 9 of 14	ENST00000255078.8	NP_002171.2	P38935

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGHMBP2	ENST00000255078.8 link	c.1418+18A>G		intron_variant	Intron 9 of 14	1	NM_002180.3	ENSP00000255078.4		P38935

Frequencies

GnomAD3 genomes

AF:

0.0595

AC:

9037

AN:

151986

Hom.:

725

Cov.:

show subpopulations

Gnomad AFR

AF:

0.183

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0318

Gnomad ASJ

AF:

0.0135

Gnomad EAS

AF:

0.0116

Gnomad SAS

AF:

0.0278

Gnomad FIN

AF:

0.00236

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.00841

Gnomad OTH

AF:

0.0566

GnomAD2 exomes

AF:

0.0227

AC:

5212

AN:

229142

AF XY:

0.0210

show subpopulations

Gnomad AFR exome

AF:

0.182

Gnomad AMR exome

AF:

0.0160

Gnomad ASJ exome

AF:

0.0194

Gnomad EAS exome

AF:

0.00517

Gnomad FIN exome

AF:

0.00309

Gnomad NFE exome

AF:

0.00857

Gnomad OTH exome

AF:

0.0205

GnomAD4 exome

AF:

0.0146

AC:

21163

AN:

1451154

Hom.:

867

Cov.:

AF XY:

0.0145

AC XY:

10431

AN XY:

721046

show subpopulations

African (AFR)

AF:

0.196

AC:

6516

AN:

33290

American (AMR)

AF:

0.0181

AC:

790

AN:

43538

Ashkenazi Jewish (ASJ)

AF:

0.0184

AC:

475

AN:

25864

East Asian (EAS)

AF:

0.0284

AC:

1117

AN:

39310

South Asian (SAS)

AF:

0.0267

AC:

2260

AN:

84668

European-Finnish (FIN)

AF:

0.00280

AC:

144

AN:

51472

Middle Eastern (MID)

AF:

0.0391

AC:

225

AN:

5750

European-Non Finnish (NFE)

AF:

0.00738

AC:

8176

AN:

1107292

Other (OTH)

AF:

0.0243

AC:

1460

AN:

59970

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

1066

2132

3198

4264

5330

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

424

848

1272

1696

2120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0597

AC:

9085

AN:

152104

Hom.:

736

Cov.:

AF XY:

0.0587

AC XY:

4362

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.184

AC:

7626

AN:

41468

American (AMR)

AF:

0.0317

AC:

484

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0135

AC:

AN:

3470

East Asian (EAS)

AF:

0.0116

AC:

AN:

5170

South Asian (SAS)

AF:

0.0278

AC:

134

AN:

4812

European-Finnish (FIN)

AF:

0.00236

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00844

AC:

574

AN:

67990

Other (OTH)

AF:

0.0598

AC:

126

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

412

824

1237

1649

2061

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

188

282

376

470

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0319

Hom.:

512

Bravo

AF:

0.0661

Asia WGS

AF:

0.0470

AC:

164

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

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

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Autosomal recessive distal spinal muscular atrophy 1;C4015349:Charcot-Marie-Tooth disease axonal type 2S

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

-0.93

CADD

Benign

0.18

(source)

DANN

Benign

0.27

PhyloP100

-4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over