Genetic Variant MATN2:p.Gly14Ala (chr8-97888141-G-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_002380.5(MATN2):c.41G>C(p.Gly14Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00112 in 1,609,544 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0060 ( 15 hom., cov: 32)

Exomes 𝑓: 0.00061 ( 8 hom. )

Consequence

MATN2
NM_002380.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.75

Publications

3 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0066571236).

BP6

Variant 8-97888141-G-C is Benign according to our data. Variant chr8-97888141-G-C is described in ClinVar as Benign. ClinVar VariationId is 778943.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00605 (921/152290) while in subpopulation AFR AF = 0.0213 (886/41564). AF 95% confidence interval is 0.0202. There are 15 homozygotes in GnomAd4. There are 456 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 15 AR gene

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	UniProt
MATN2	NM_002380.5	MANE Select	c.41G>C	p.Gly14Ala	missense	Exon 2 of 19	NP_002371.3
MATN2	NM_030583.4		c.41G>C	p.Gly14Ala	missense	Exon 2 of 19	NP_085072.2	O00339-2
MATN2	NM_001317748.2		c.41G>C	p.Gly14Ala	missense	Exon 2 of 18	NP_001304677.1	O00339-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MATN2	ENST00000254898.7	TSL:1 MANE Select	c.41G>C	p.Gly14Ala	missense	Exon 2 of 19	ENSP00000254898.6	O00339-1
MATN2	ENST00000520016.5	TSL:1	c.41G>C	p.Gly14Ala	missense	Exon 1 of 18	ENSP00000430487.1	O00339-1
MATN2	ENST00000521689.5	TSL:1	c.41G>C	p.Gly14Ala	missense	Exon 2 of 19	ENSP00000429977.1	O00339-2

Frequencies

GnomAD3 genomes

AF:

0.00603

AC:

918

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0213

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00177

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:

0.0000588

Gnomad OTH

AF:

0.00191

GnomAD2 exomes

AF:

0.00148

AC:

361

AN:

244390

AF XY:

0.00108

show subpopulations

Gnomad AFR exome

AF:

0.0214

Gnomad AMR exome

AF:

0.000882

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000179

Gnomad OTH exome

AF:

0.000683

GnomAD4 exome

AF:

0.000609

AC:

887

AN:

1457254

Hom.:

Cov.:

AF XY:

0.000494

AC XY:

358

AN XY:

724862

show subpopulations

African (AFR)

AF:

0.0211

AC:

701

AN:

33218

American (AMR)

AF:

0.000959

AC:

AN:

43814

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26050

East Asian (EAS)

AF:

0.00

AC:

AN:

39378

South Asian (SAS)

AF:

0.0000117

AC:

AN:

85332

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53332

Middle Eastern (MID)

AF:

0.000349

AC:

AN:

5738

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

1110186

Other (OTH)

AF:

0.00153

AC:

AN:

60206

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

143

190

238

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

130

<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:

0.00605

AC:

921

AN:

152290

Hom.:

Cov.:

AF XY:

0.00612

AC XY:

456

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.0213

AC:

886

AN:

41564

American (AMR)

AF:

0.00176

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68018

Other (OTH)

AF:

0.00189

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

142

189

236

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.000998

Hom.:

Bravo

AF:

0.00670

ESP6500AA

AF:

0.0200

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00196

AC:

237

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.14

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.023

Eigen

Benign

-0.082

Eigen_PC

Benign

-0.033

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.81

MetaRNN

Benign

0.0067

MetaSVM

Benign

-0.53

MutationAssessor

Benign

0.55

PhyloP100

1.7

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.22

REVEL

Uncertain

0.30

Sift

Benign

0.089

Sift4G

Benign

0.66

Polyphen

0.79

Vest4

0.26

MVP

0.88

MPC

0.21

ClinPred

0.014

GERP RS

5.0

PromoterAI

0.0073

Neutral

(source)

Varity_R

0.063

gMVP

0.57

Mutation Taster

=100/0

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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