8-97931175-G-A

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_002380.5(MATN2):c.365G>A(p.Arg122His) variant causes a missense change. The variant allele was found at a frequency of 0.0000105 in 1,613,422 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

MATN2
NM_002380.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.18

Variant links:

Genes affected

MATN2 (HGNC:6908): (matrilin 2) This gene encodes a member of the von Willebrand factor A domain containing protein family. This family of proteins is thought to be involved in the formation of filamentous networks in the extracellular matrices of various tissues. This protein contains five von Willebrand factor A domains. The specific function of this gene has not yet been determined. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

MATN2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.41507366).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MATN2	NM_002380.5 link	c.365G>A	p.Arg122His	missense_variant	Exon 3 of 19	ENST00000254898.7	NP_002371.3	O00339-1A0A140VKH7Q8N2G3
MATN2	NM_030583.4 link	c.365G>A	p.Arg122His	missense_variant	Exon 3 of 19		NP_085072.2	O00339-2Q8N2G3
MATN2	NM_001317748.2 link	c.365G>A	p.Arg122His	missense_variant	Exon 3 of 18		NP_001304677.1	O00339-3Q8N2G3
MATN2	XM_005250920.3 link	c.365G>A	p.Arg122His	missense_variant	Exon 3 of 18		XP_005250977.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MATN2	ENST00000254898.7 link	c.365G>A	p.Arg122His	missense_variant	Exon 3 of 19	1	NM_002380.5	ENSP00000254898.6	O00339-1
MATN2	ENST00000520016.5 link	c.365G>A	p.Arg122His	missense_variant	Exon 2 of 18	1		ENSP00000430487.1	O00339-1
MATN2	ENST00000521689.5 link	c.365G>A	p.Arg122His	missense_variant	Exon 3 of 19	1		ENSP00000429977.1	O00339-2
MATN2	ENST00000524308.5 link	c.365G>A	p.Arg122His	missense_variant	Exon 3 of 18	1		ENSP00000430221.1	O00339-3
MATN2	ENST00000522025.6 link	c.-115+635G>A		intron_variant	Intron 2 of 17	5		ENSP00000429010.1	O00339-4
MATN2	ENST00000518154.5 link	c.-167G>A		upstream_gene_variant		1		ENSP00000429622.1	H0YBJ4

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000109

AC:

AN:

1461230

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

726838

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

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:

0.0000108

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152192

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000312

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 04, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.365G>A (p.R122H) alteration is located in exon 3 (coding exon 2) of the MATN2 gene. This alteration results from a G to A substitution at nucleotide position 365, causing the arginine (R) at amino acid position 122 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.016

BayesDel_noAF

Benign

-0.26

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.32

.;T;.;T

Eigen

Pathogenic

0.68

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.92

D;D;D;.

M_CAP

Uncertain

0.089

MetaRNN

Benign

0.42

T;T;T;T

MetaSVM

Uncertain

0.24

MutationAssessor

Benign

2.0

M;M;M;M

PrimateAI

Benign

0.41

PROVEAN

Uncertain

-3.0

D;D;D;D

REVEL

Uncertain

0.55

Sift

Uncertain

0.015

D;D;D;D

Sift4G

Uncertain

0.0060

D;D;D;D

Polyphen

1.0

D;D;.;D

Vest4

0.22

MutPred

0.54

Loss of methylation at K125 (P = 0.0613);Loss of methylation at K125 (P = 0.0613);Loss of methylation at K125 (P = 0.0613);Loss of methylation at K125 (P = 0.0613);

MVP

0.95

MPC

0.27

ClinPred

0.99

GERP RS

5.1

Varity_R

0.20

gMVP

0.55

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

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