11-68903988-G-T

Position:

• chr11-68903988-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002180.3(IGHMBP2):​c.36G>T​(p.Lys12Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 35)
• Consequence: IGHMBP2 NM_002180.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.46

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30374998).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGHMBP2	NM_002180.3	c.36G>T	p.Lys12Asn	missense_variant	1/15	ENST00000255078.8	NP_002171.2
IGHMBP2	XM_047426881.1	c.36G>T	p.Lys12Asn	missense_variant	1/15		XP_047282837.1
IGHMBP2	XM_017017671.3	c.36G>T	p.Lys12Asn	missense_variant	1/12		XP_016873160.1
IGHMBP2	XM_005273976.3	c.36G>T	p.Lys12Asn	missense_variant	1/9		XP_005274033.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGHMBP2	ENST00000255078.8	c.36G>T	p.Lys12Asn	missense_variant	1/15	1	NM_002180.3	ENSP00000255078.4

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome Cov.: 44

GnomAD4 genome Cov.: 35

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Charcot-Marie-Tooth disease Benign:1

Benign, criteria provided, single submitter

clinical testing

Molecular Genetics Laboratory, London Health Sciences Centre

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.070	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	T;.
Eigen	Benign	-0.060
Eigen_PC	Benign	-0.028
FATHMM_MKL	Benign	0.072	N
LIST_S2	Benign	0.85	T;D
M_CAP	Pathogenic	0.48	D
MetaRNN	Benign	0.30	T;T
MetaSVM	Uncertain	-0.27	T
MutationAssessor	Uncertain	2.4	M;.
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-2.0	N;D
REVEL	Benign	0.20
Sift	Benign	0.086	T;T
Sift4G	Benign	0.22	T;D
Polyphen		0.41	B;.
Vest4		0.23
MutPred		0.43		Loss of ubiquitination at K12 (P = 0.0255);Loss of ubiquitination at K12 (P = 0.0255);
MVP		0.93
MPC		0.56
ClinPred		0.90	D
GERP RS		2.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.26
gMVP		0.52

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

Other links and lift over

dbSNP: rs1858067155; hg19: chr11-68671456;