11-118260334-T-C

Variant names:

• chr11-118260334-T-C
• rs17121997
• NM_005797.4:c.437-133A>G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005797.4(MPZL2):​c.437-133A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.5 in 866,406 control chromosomes in the GnomAD database, including 114,498 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.42 (15078 hom., cov: 32)
  • Exomes 𝑓: 0.52 (99420 hom.)
• Consequence: MPZL2 NM_005797.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0690

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 11-118260334-T-C is Benign according to our data. Variant chr11-118260334-T-C is described in ClinVar as [Benign]. Clinvar id is 1278235.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.703 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MPZL2	NM_005797.4	c.437-133A>G		intron_variant	Intron 3 of 5	ENST00000278937.7	NP_005788.1
MPZL2	NM_144765.3	c.437-133A>G		intron_variant	Intron 3 of 4		NP_658911.1
MPZL2	XM_047426229.1	c.373-133A>G		intron_variant	Intron 3 of 3		XP_047282185.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MPZL2	ENST00000278937.7	c.437-133A>G		intron_variant	Intron 3 of 5	1	NM_005797.4	ENSP00000278937.2
MPZL2	ENST00000438295.2	c.437-133A>G		intron_variant	Intron 3 of 4	1		ENSP00000408362.2
MPZL2	ENST00000529376.5	n.567-133A>G		intron_variant	Intron 3 of 3	2
MPZL2	ENST00000534175.6	n.485-133A>G		intron_variant	Intron 2 of 4	5

Frequencies

GnomAD3 genomes AF: 0.417 AC: 63343 AN: 151964 Hom.: 15071 Cov.: 32

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.482

Gnomad AMR AF: 0.408

Gnomad ASJ AF: 0.500

Gnomad EAS AF: 0.564

Gnomad SAS AF: 0.723

Gnomad FIN AF: 0.508

Gnomad MID AF: 0.376

Gnomad NFE AF: 0.510

Gnomad OTH AF: 0.436

GnomAD4 exome AF: 0.518 AC: 370076 AN: 714324 Hom.: 99420 AF XY: 0.528 AC XY: 192667 AN XY: 365152

Gnomad4 AFR exome AF: 0.170

Gnomad4 AMR exome AF: 0.425

Gnomad4 ASJ exome AF: 0.510

Gnomad4 EAS exome AF: 0.602

Gnomad4 SAS exome AF: 0.717

Gnomad4 FIN exome AF: 0.490

Gnomad4 NFE exome AF: 0.512

Gnomad4 OTH exome AF: 0.499

GnomAD4 genome AF: 0.417 AC: 63378 AN: 152082 Hom.: 15078 Cov.: 32 AF XY: 0.419 AC XY: 31164 AN XY: 74334

Gnomad4 AFR AF: 0.180

Gnomad4 AMR AF: 0.409

Gnomad4 ASJ AF: 0.500

Gnomad4 EAS AF: 0.565

Gnomad4 SAS AF: 0.723

Gnomad4 FIN AF: 0.508

Gnomad4 NFE AF: 0.510

Gnomad4 OTH AF: 0.436

Alfa AF: 0.443 Hom.: 2005

Bravo AF: 0.397

Asia WGS AF: 0.609 AC: 2120 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 13, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.3
DANN	Benign	0.39

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: rs17121997; hg19: chr11-118131049; COSMIC: COSV54048458; COSMIC: COSV54048458;