11-118262532-C-G

Variant names:

• chr11-118262532-C-G
• rs1372867800
• NM_005797.4:c.342G>C

Variant summary

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

The NM_005797.4(MPZL2):​c.342G>C​(p.Gln114His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MPZL2 NM_005797.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.57

Genes affected

MPZL2 (HGNC:3496): (myelin protein zero like 2) Thymus development depends on a complex series of interactions between thymocytes and the stromal component of the organ. Epithelial V-like antigen (EVA) is expressed in thymus epithelium and strongly downregulated by thymocyte developmental progression. This gene is expressed in the thymus and in several epithelial structures early in embryogenesis. It is highly homologous to the myelin protein zero and, in thymus-derived epithelial cell lines, is poorly soluble in nonionic detergents, strongly suggesting an association to the cytoskeleton. Its capacity to mediate cell adhesion through a homophilic interaction and its selective regulation by T cell maturation might imply the participation of EVA in the earliest phases of thymus organogenesis. The protein bears a characteristic V-type domain and two potential N-glycosylation sites in the extracellular domain; a putative serine phosphorylation site for casein kinase 2 is also present in the cytoplasmic tail. Two transcript variants encoding the same protein have been found for this gene. [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 rank	MANE	Protein	UniProt
MPZL2	NM_005797.4	c.342G>C	p.Gln114His	missense_variant	Exon 3 of 6	ENST00000278937.7	NP_005788.1
MPZL2	NM_144765.3	c.342G>C	p.Gln114His	missense_variant	Exon 3 of 5		NP_658911.1
MPZL2	XM_047426229.1	c.342G>C	p.Gln114His	missense_variant	Exon 3 of 4		XP_047282185.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MPZL2	ENST00000278937.7	c.342G>C	p.Gln114His	missense_variant	Exon 3 of 6	1	NM_005797.4	ENSP00000278937.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000301 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.016	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.45	T;T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.67	.;T
M_CAP	Uncertain	0.090	D
MetaRNN	Uncertain	0.54	D;D
MetaSVM	Uncertain	-0.27	T
MutationAssessor	Uncertain	2.5	M;M
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-2.6	D;D
REVEL	Uncertain	0.43
Sift	Benign	0.033	D;D
Sift4G	Benign	0.062	T;T
Polyphen		0.81	P;P
Vest4		0.43
MutPred		0.62		Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);
MVP		0.63
MPC		0.082
ClinPred		0.99	D
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.27
gMVP		0.75

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: rs1372867800; hg19: chr11-118133247;