rs200089714

chr11-68906109-C-Gchr11-68906109-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002180.3(IGHMBP2):c.127C>G(p.Arg43Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R43Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: IGHMBP2 NM_002180.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.58

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IGHMBP2	NM_002180.3	c.127C>G	p.Arg43Gly	missense_variant	2/15	ENST00000255078.8
IGHMBP2	XM_047426881.1	c.127C>G	p.Arg43Gly	missense_variant	2/15
IGHMBP2	XM_017017671.3	c.127C>G	p.Arg43Gly	missense_variant	2/12
IGHMBP2	XM_005273976.3	c.127C>G	p.Arg43Gly	missense_variant	2/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IGHMBP2	ENST00000255078.8	c.127C>G	p.Arg43Gly	missense_variant	2/15	1	NM_002180.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.11
Cadd	Benign	23
Dann	Uncertain	1.0
DEOGEN2	Benign	0.41	T;.
Eigen	Uncertain	0.19
Eigen_PC	Benign	0.16
FATHMM_MKL	Benign	0.73	D
LIST_S2	Uncertain	0.93	D;D
M_CAP	Uncertain	0.12	D
MetaRNN	Uncertain	0.59	D;D
MetaSVM	Uncertain	0.30	D
MutationAssessor	Uncertain	2.6	M;.
MutationTaster	Benign	0.91	D;D
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-4.2	D;D
REVEL	Uncertain	0.57
Sift	Uncertain	0.0060	D;D
Sift4G	Uncertain	0.045	D;D
Polyphen		0.65	P;.
Vest4		0.62
MutPred		0.57		Loss of MoRF binding (P = 0.0213);Loss of MoRF binding (P = 0.0213);
MVP		0.95
MPC		0.50
ClinPred		0.98	D
GERP RS		2.4
Varity_R		0.41
gMVP		0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs200089714; hg19: chr11-68673577;