11-68908165-G-C

Position:

• chr11-68908165-G-C

Variant summary

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

The NM_002180.3(IGHMBP2):​c.277G>C​(p.Asp93His) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,826 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: IGHMBP2 NM_002180.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.18

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 (HGNC:):

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	Protein	UniProt
IGHMBP2	NM_002180.3	c.277G>C	p.Asp93His	missense_variant	3/15	ENST00000255078.8	NP_002171.2
IGHMBP2	XM_047426881.1	c.277G>C	p.Asp93His	missense_variant	3/15		XP_047282837.1
IGHMBP2	XM_017017671.3	c.277G>C	p.Asp93His	missense_variant	3/12		XP_016873160.1
IGHMBP2	XM_005273976.3	c.277G>C	p.Asp93His	missense_variant	3/9		XP_005274033.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGHMBP2	ENST00000255078.8	c.277G>C	p.Asp93His	missense_variant	3/15	1	NM_002180.3	ENSP00000255078.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251354 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135860

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461826 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727214

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Uncertain	0.058	T
BayesDel_noAF	Uncertain	-0.060
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T;.
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.78	T;T
M_CAP	Benign	0.085	D
MetaRNN	Uncertain	0.53	D;D
MetaSVM	Uncertain	0.64	D
MutationAssessor	Uncertain	2.2	M;.
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-1.8	N;N
REVEL	Uncertain	0.47
Sift	Uncertain	0.024	D;T
Sift4G	Benign	0.10	T;T
Polyphen		0.93	P;.
Vest4		0.34
MutPred		0.46		Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);
MVP		0.94
MPC		0.30
ClinPred		0.68	D
GERP RS		4.0
Varity_R		0.15
gMVP		0.48

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: rs200897747; hg19: chr11-68675633; COSMIC: COSV54820104; COSMIC: COSV54820104;