11-118262458-C-T

Position:

chr11-118262458-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_005797.4(MPZL2):c.416G>A(p.Arg139Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00108 in 1,614,018 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.00093 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 29 hom. )

Consequence

MPZL2
NM_005797.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.226

Variant links:

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]

MPZL2 links:

MPZL2 (HGNC:):

MPZL2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007665932).

BP6

Variant 11-118262458-C-T is Benign according to our data. Variant chr11-118262458-C-T is described in ClinVar as [Benign]. Clinvar id is 3033516.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-118262458-C-T is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000932 (142/152306) while in subpopulation EAS AF= 0.0235 (122/5182). AF 95% confidence interval is 0.0201. There are 2 homozygotes in gnomad4. There are 75 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MPZL2	NM_005797.4 linkuse as main transcript	c.416G>A	p.Arg139Gln	missense_variant	3/6	ENST00000278937.7	NP_005788.1	O60487A0A024R3K1
MPZL2	NM_144765.3 linkuse as main transcript	c.416G>A	p.Arg139Gln	missense_variant	3/5		NP_658911.1	O60487A0A024R3K1
MPZL2	XM_047426229.1 linkuse as main transcript	c.372+44G>A		intron_variant			XP_047282185.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MPZL2	ENST00000278937.7 linkuse as main transcript	c.416G>A	p.Arg139Gln	missense_variant	3/6	1	NM_005797.4	ENSP00000278937.2		O60487

Frequencies

GnomAD3 genomes

AF:

0.000926

AC:

141

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0235

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000565

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.00147

AC:

370

AN:

250932

Hom.:

AF XY:

0.00152

AC XY:

206

AN XY:

135648

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.000260

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0162

Gnomad SAS exome

AF:

0.00111

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.000132

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.00109

AC:

1598

AN:

1461712

Hom.:

Cov.:

AF XY:

0.00112

AC XY:

818

AN XY:

727162

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000246

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0294

Gnomad4 SAS exome

AF:

0.00101

Gnomad4 FIN exome

AF:

0.000131

Gnomad4 NFE exome

AF:

0.000104

Gnomad4 OTH exome

AF:

0.00330

GnomAD4 genome

AF:

0.000932

AC:

142

AN:

152306

Hom.:

Cov.:

AF XY:

0.00101

AC XY:

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0235

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000565

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00127

Hom.:

Bravo

AF:

0.000933

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000778

AC:

ExAC

AF:

0.00159

AC:

193

Asia WGS

AF:

0.0160

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

MPZL2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 06, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.094

T;T

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.54

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.85

.;T

MetaRNN

Benign

0.0077

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.88

L;L

PrimateAI

Benign

0.20

PROVEAN

Benign

-0.43

N;N

REVEL

Benign

0.070

Sift

Benign

0.29

T;T

Sift4G

Benign

0.39

T;T

Polyphen

0.010

B;B

Vest4

0.15

MVP

0.48

MPC

0.065

ClinPred

0.028

GERP RS

1.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.092

gMVP

0.50

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over