8-97931174-C-A

Variant names:

Variant summary

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

The NM_002380.5(MATN2):c.364C>A(p.Arg122Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,613,386 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: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

MATN2
NM_002380.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.969

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 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
MATN2	NM_002380.5 link	c.364C>A	p.Arg122Ser	missense_variant	Exon 3 of 19	ENST00000254898.7	NP_002371.3	O00339-1A0A140VKH7Q8N2G3
MATN2	NM_030583.4 link	c.364C>A	p.Arg122Ser	missense_variant	Exon 3 of 19		NP_085072.2	O00339-2Q8N2G3
MATN2	NM_001317748.2 link	c.364C>A	p.Arg122Ser	missense_variant	Exon 3 of 18		NP_001304677.1	O00339-3Q8N2G3
MATN2	XM_005250920.3 link	c.364C>A	p.Arg122Ser	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.364C>A	p.Arg122Ser	missense_variant	Exon 3 of 19	1	NM_002380.5	ENSP00000254898.6	O00339-1
MATN2	ENST00000520016.5 link	c.364C>A	p.Arg122Ser	missense_variant	Exon 2 of 18	1		ENSP00000430487.1	O00339-1
MATN2	ENST00000521689.5 link	c.364C>A	p.Arg122Ser	missense_variant	Exon 3 of 19	1		ENSP00000429977.1	O00339-2
MATN2	ENST00000524308.5 link	c.364C>A	p.Arg122Ser	missense_variant	Exon 3 of 18	1		ENSP00000430221.1	O00339-3
MATN2	ENST00000522025.6 link	c.-115+634C>A		intron_variant	Intron 2 of 17	5		ENSP00000429010.1	O00339-4
MATN2	ENST00000518154.5 link	c.-168C>A		upstream_gene_variant		1		ENSP00000429622.1	H0YBJ4

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

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

GnomAD3 exomes

AF:

0.00000805

AC:

AN:

248484

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

134768

show subpopulations

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:

0.0000655

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461122

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726794

show subpopulations

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:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152264

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 10, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.364C>A (p.R122S) alteration is located in exon 3 (coding exon 2) of the MATN2 gene. This alteration results from a C to A substitution at nucleotide position 364, causing the arginine (R) at amino acid position 122 to be replaced by a serine (S). 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

Uncertain

0.49

BayesDel_addAF

Benign

-0.090

BayesDel_noAF

Benign

-0.19

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.27

.;T;.;T

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Benign

0.72

LIST_S2

Uncertain

0.95

D;D;D;.

M_CAP

Uncertain

0.15

MetaRNN

Uncertain

0.47

T;T;T;T

MetaSVM

Uncertain

0.022

MutationAssessor

Benign

0.93

L;L;L;L

PrimateAI

Benign

0.40

PROVEAN

Uncertain

-3.1

D;D;D;D

REVEL

Uncertain

0.50

Sift

Uncertain

0.0030

D;D;D;D

Sift4G

Uncertain

0.0050

D;D;D;D

Polyphen

1.0

D;D;.;D

Vest4

0.54

MutPred

0.45

Gain of phosphorylation at R122 (P = 0.0477);Gain of phosphorylation at R122 (P = 0.0477);Gain of phosphorylation at R122 (P = 0.0477);Gain of phosphorylation at R122 (P = 0.0477);

MVP

0.93

MPC

0.59

ClinPred

0.94

GERP RS

4.0

Varity_R

0.45

gMVP

0.68

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