chr8-97941777-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_002380.5(MATN2):c.713C>T(p.Thr238Met) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000128 in 1,586,000 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 18/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00013 ( 2 hom. )

Consequence

MATN2
NM_002380.5 missense, splice_region

Scores

Splicing: ADA: 0.0001921

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.240

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.024647057).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MATN2	NM_002380.5 link	c.713C>T	p.Thr238Met	missense_variant, splice_region_variant	Exon 4 of 19	ENST00000254898.7	NP_002371.3	O00339-1A0A140VKH7Q8N2G3
MATN2	NM_030583.4 link	c.713C>T	p.Thr238Met	missense_variant, splice_region_variant	Exon 4 of 19		NP_085072.2	O00339-2Q8N2G3
MATN2	NM_001317748.2 link	c.713C>T	p.Thr238Met	missense_variant, splice_region_variant	Exon 4 of 18		NP_001304677.1	O00339-3Q8N2G3
MATN2	XM_005250920.3 link	c.713C>T	p.Thr238Met	missense_variant, splice_region_variant	Exon 4 of 18		XP_005250977.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MATN2	ENST00000254898.7 link	c.713C>T	p.Thr238Met	missense_variant, splice_region_variant	Exon 4 of 19	1	NM_002380.5	ENSP00000254898.6	O00339-1
MATN2	ENST00000520016.5 link	c.713C>T	p.Thr238Met	missense_variant, splice_region_variant	Exon 3 of 18	1		ENSP00000430487.1	O00339-1
MATN2	ENST00000521689.5 link	c.713C>T	p.Thr238Met	missense_variant, splice_region_variant	Exon 4 of 19	1		ENSP00000429977.1	O00339-2
MATN2	ENST00000524308.5 link	c.713C>T	p.Thr238Met	missense_variant, splice_region_variant	Exon 4 of 18	1		ENSP00000430221.1	O00339-3
MATN2	ENST00000518154.5 link	c.182C>T	p.Thr61Met	missense_variant, splice_region_variant	Exon 2 of 16	1		ENSP00000429622.1	H0YBJ4
MATN2	ENST00000522025.6 link	c.-114-26C>T		intron_variant	Intron 2 of 17	5		ENSP00000429010.1	O00339-4

Frequencies

GnomAD3 genomes

AF:

0.000125

AC:

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000153

AC:

AN:

209346

Hom.:

AF XY:

0.000169

AC XY:

AN XY:

112316

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000138

Gnomad ASJ exome

AF:

0.000107

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000495

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000152

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000128

AC:

184

AN:

1433736

Hom.:

Cov.:

AF XY:

0.000132

AC XY:

AN XY:

710578

show subpopulations

Gnomad4 AFR exome

AF:

0.000182

Gnomad4 AMR exome

AF:

0.000203

Gnomad4 ASJ exome

AF:

0.000156

Gnomad4 EAS exome

AF:

0.0000260

Gnomad4 SAS exome

AF:

0.000619

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000947

Gnomad4 OTH exome

AF:

0.000118

GnomAD4 genome

AF:

0.000125

AC:

AN:

152264

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.0000962

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000160

Hom.:

Bravo

AF:

0.0000982

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000118

AC:

ExAC

AF:

0.000190

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 22, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.713C>T (p.T238M) alteration is located in exon 4 (coding exon 3) of the MATN2 gene. This alteration results from a C to T substitution at nucleotide position 713, causing the threonine (T) at amino acid position 238 to be replaced by a methionine (M). 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

0.071

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.40

CADD

Benign

4.1

DANN

Benign

0.84

DEOGEN2

Benign

0.034

.;T;.;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.027

LIST_S2

Benign

0.29

T;T;T;.

M_CAP

Benign

0.051

MetaRNN

Benign

0.025

T;T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.55

N;N;N;N

PrimateAI

Benign

0.22

PROVEAN

Benign

-1.0

N;N;N;N

REVEL

Benign

0.21

Sift

Benign

0.047

D;T;T;D

Sift4G

Benign

0.13

T;T;T;T

Polyphen

0.012

B;B;.;B

Vest4

0.080

MVP

0.60

MPC

0.20

ClinPred

0.036

GERP RS

-2.7

Varity_R

0.026

gMVP

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00019

dbscSNV1_RF

Benign

0.12

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