Variant 8-97931192-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_002380.5(MATN2):c.382C>T(p.Arg128Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,460,516 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

MATN2
NM_002380.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.498

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:

MATN2 (HGNC:):

MATN2 links:

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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/exons	MANE	Protein	UniProt
MATN2	NM_002380.5 linkuse as main transcript	c.382C>T	p.Arg128Trp	missense_variant	3/19	ENST00000254898.7	NP_002371.3	O00339-1A0A140VKH7Q8N2G3
MATN2	NM_030583.4 linkuse as main transcript	c.382C>T	p.Arg128Trp	missense_variant	3/19		NP_085072.2	O00339-2Q8N2G3
MATN2	NM_001317748.2 linkuse as main transcript	c.382C>T	p.Arg128Trp	missense_variant	3/18		NP_001304677.1	O00339-3Q8N2G3
MATN2	XM_005250920.3 linkuse as main transcript	c.382C>T	p.Arg128Trp	missense_variant	3/18		XP_005250977.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MATN2	ENST00000254898.7 linkuse as main transcript	c.382C>T	p.Arg128Trp	missense_variant	3/19	1	NM_002380.5	ENSP00000254898.6	O00339-1
MATN2	ENST00000520016.5 linkuse as main transcript	c.382C>T	p.Arg128Trp	missense_variant	2/18	1		ENSP00000430487.1	O00339-1
MATN2	ENST00000521689.5 linkuse as main transcript	c.382C>T	p.Arg128Trp	missense_variant	3/19	1		ENSP00000429977.1	O00339-2
MATN2	ENST00000524308.5 linkuse as main transcript	c.382C>T	p.Arg128Trp	missense_variant	3/18	1		ENSP00000430221.1	O00339-3
MATN2	ENST00000522025.6 linkuse as main transcript	c.-115+652C>T		intron_variant		5		ENSP00000429010.1	O00339-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000403

AC:

AN:

248224

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134622

show subpopulations

Gnomad AFR exome

AF:

0.0000646

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1460516

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

726348

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.00000630

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ESP6500AA

AF:

0.000235

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00000826

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 22, 2023

The c.382C>T (p.R128W) alteration is located in exon 3 (coding exon 2) of the MATN2 gene. This alteration results from a C to T substitution at nucleotide position 382, causing the arginine (R) at amino acid position 128 to be replaced by a tryptophan (W). 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

0.18

BayesDel_addAF

Uncertain

0.035

BayesDel_noAF

Benign

-0.19

CADD

Benign

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.38

.;T;.;T

Eigen

Uncertain

0.27

Eigen_PC

Benign

0.21

FATHMM_MKL

Uncertain

0.76

LIST_S2

Uncertain

0.96

D;D;D;.

M_CAP

Benign

0.050

MetaRNN

Uncertain

0.49

T;T;T;T

MetaSVM

Uncertain

0.12

MutationAssessor

Benign

1.9

L;L;L;L

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-1.1

N;N;N;N

REVEL

Uncertain

0.49

Sift

Uncertain

0.017

D;D;D;D

Sift4G

Uncertain

0.017

D;D;D;D

Polyphen

1.0

D;D;.;D

Vest4

0.41

MVP

0.93

MPC

0.72

ClinPred

0.73

GERP RS

0.81

Varity_R

0.14

gMVP

0.61

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