8-98032300-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002380.5(MATN2):c.2564C>T(p.Thr855Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 1,609,336 control chromosomes in the GnomAD database, including 11,045 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.12 ( 1072 hom., cov: 32)

Exomes 𝑓: 0.11 ( 9973 hom. )

Consequence

MATN2
NM_002380.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.258

Publications

22 publications found

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:

RPL30 (HGNC:10333): (ribosomal protein L30) Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 60S subunit. The protein belongs to the L30E family of ribosomal proteins. It is located in the cytoplasm. This gene is co-transcribed with the U72 small nucleolar RNA gene, which is located in its fourth intron. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Jul 2008]

RPL30 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0012082458).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002380.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
MATN2	NM_002380.5	MANE Select	c.2564C>T	p.Thr855Met	missense	Exon 16 of 19	NP_002371.3
MATN2	NM_030583.4		c.2564C>T	p.Thr855Met	missense	Exon 16 of 19	NP_085072.2
MATN2	NM_001317748.2		c.2441C>T	p.Thr814Met	missense	Exon 15 of 18	NP_001304677.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
MATN2	ENST00000254898.7	TSL:1 MANE Select	c.2564C>T	p.Thr855Met	missense	Exon 16 of 19	ENSP00000254898.6
MATN2	ENST00000520016.5	TSL:1	c.2564C>T	p.Thr855Met	missense	Exon 15 of 18	ENSP00000430487.1
MATN2	ENST00000521689.5	TSL:1	c.2564C>T	p.Thr855Met	missense	Exon 16 of 19	ENSP00000429977.1

Frequencies

GnomAD3 genomes

AF:

0.116

AC:

17693

AN:

152036

Hom.:

1066

Cov.:

show subpopulations

Gnomad AFR

AF:

0.115

Gnomad AMI

AF:

0.0844

Gnomad AMR

AF:

0.138

Gnomad ASJ

AF:

0.176

Gnomad EAS

AF:

0.191

Gnomad SAS

AF:

0.0922

Gnomad FIN

AF:

0.0817

Gnomad MID

AF:

0.108

Gnomad NFE

AF:

0.111

Gnomad OTH

AF:

0.126

GnomAD2 exomes

AF:

0.121

AC:

29293

AN:

242656

AF XY:

0.117

show subpopulations

Gnomad AFR exome

AF:

0.112

Gnomad AMR exome

AF:

0.173

Gnomad ASJ exome

AF:

0.162

Gnomad EAS exome

AF:

0.193

Gnomad FIN exome

AF:

0.0818

Gnomad NFE exome

AF:

0.106

Gnomad OTH exome

AF:

0.104

GnomAD4 exome

AF:

0.114

AC:

165420

AN:

1457182

Hom.:

9973

Cov.:

AF XY:

0.113

AC XY:

81841

AN XY:

724548

show subpopulations

African (AFR)

AF:

0.111

AC:

3701

AN:

33426

American (AMR)

AF:

0.168

AC:

7380

AN:

43980

Ashkenazi Jewish (ASJ)

AF:

0.167

AC:

4356

AN:

26038

East Asian (EAS)

AF:

0.175

AC:

6907

AN:

39568

South Asian (SAS)

AF:

0.0990

AC:

8468

AN:

85542

European-Finnish (FIN)

AF:

0.0825

AC:

4390

AN:

53194

Middle Eastern (MID)

AF:

0.136

AC:

782

AN:

5762

European-Non Finnish (NFE)

AF:

0.110

AC:

122456

AN:

1109440

Other (OTH)

AF:

0.116

AC:

6980

AN:

60232

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.448

Heterozygous variant carriers

6987

13974

20960

27947

34934

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4612

9224

13836

18448

23060

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.116

AC:

17709

AN:

152154

Hom.:

1072

Cov.:

AF XY:

0.117

AC XY:

8667

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.115

AC:

4787

AN:

41504

American (AMR)

AF:

0.138

AC:

2106

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.176

AC:

609

AN:

3468

East Asian (EAS)

AF:

0.191

AC:

985

AN:

5160

South Asian (SAS)

AF:

0.0925

AC:

446

AN:

4820

European-Finnish (FIN)

AF:

0.0817

AC:

865

AN:

10586

Middle Eastern (MID)

AF:

0.102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.111

AC:

7540

AN:

67996

Other (OTH)

AF:

0.125

AC:

264

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

786

1572

2358

3144

3930

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

198

396

594

792

990

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.116

Hom.:

5263

Bravo

AF:

0.123

TwinsUK

AF:

0.108

AC:

402

ALSPAC

AF:

0.117

AC:

449

ESP6500AA

AF:

0.121

AC:

452

ESP6500EA

AF:

0.108

AC:

888

ExAC

AF:

0.115

AC:

13865

Asia WGS

AF:

0.135

AC:

473

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.35

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.037

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.049

LIST_S2

Benign

0.21

MetaRNN

Benign

0.0012

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.20

PhyloP100

-0.26

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.55

REVEL

Benign

0.21

Sift

Benign

0.091

Sift4G

Benign

0.099

Polyphen

0.010

Vest4

0.018

MPC

0.20

ClinPred

0.0055

GERP RS

-0.47

PromoterAI

-0.0058

Neutral

(source)

Varity_R

0.013

gMVP

0.31

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over