8-98027545-C-T

Position:

chr8-98027545-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_002380.5(MATN2):c.2072C>T(p.Ala691Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000806 in 1,613,804 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

MATN2
NM_002380.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.56

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:):

RPL30 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.26903737).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MATN2	NM_002380.5 linkuse as main transcript	c.2072C>T	p.Ala691Val	missense_variant	14/19	ENST00000254898.7	NP_002371.3	O00339-1A0A140VKH7Q8N2G3
MATN2	NM_030583.4 linkuse as main transcript	c.2072C>T	p.Ala691Val	missense_variant	14/19		NP_085072.2	O00339-2Q8N2G3
MATN2	NM_001317748.2 linkuse as main transcript	c.1949C>T	p.Ala650Val	missense_variant	13/18		NP_001304677.1	O00339-3Q8N2G3
MATN2	XM_005250920.3 linkuse as main transcript	c.1943-2917C>T		intron_variant			XP_005250977.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MATN2	ENST00000254898.7 linkuse as main transcript	c.2072C>T	p.Ala691Val	missense_variant	14/19	1	NM_002380.5	ENSP00000254898.6	O00339-1
MATN2	ENST00000520016.5 linkuse as main transcript	c.2072C>T	p.Ala691Val	missense_variant	13/18	1		ENSP00000430487.1	O00339-1
MATN2	ENST00000521689.5 linkuse as main transcript	c.2072C>T	p.Ala691Val	missense_variant	14/19	1		ENSP00000429977.1	O00339-2
MATN2	ENST00000524308.5 linkuse as main transcript	c.1949C>T	p.Ala650Val	missense_variant	13/18	1		ENSP00000430221.1	O00339-3
MATN2	ENST00000518154.5 linkuse as main transcript	c.1418C>T	p.Ala473Val	missense_variant	11/16	1		ENSP00000429622.1	H0YBJ4
MATN2	ENST00000522025.6 linkuse as main transcript	c.1220C>T	p.Ala407Val	missense_variant	13/18	5		ENSP00000429010.1	O00339-4
MATN2	ENST00000521952.5 linkuse as main transcript	n.*25-2917C>T		intron_variant		5		ENSP00000429256.1	H0YBD5

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152108

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000401

AC:

AN:

249228

Hom.:

AF XY:

0.0000370

AC XY:

AN XY:

135206

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000261

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:

0.000165

GnomAD4 exome

AF:

0.00000753

AC:

AN:

1461696

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727128

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152108

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74288

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ExAC

AF:

0.0000579

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

Dec 03, 2024

The c.2072C>T (p.A691V) alteration is located in exon 14 (coding exon 13) of the MATN2 gene. This alteration results from a C to T substitution at nucleotide position 2072, causing the alanine (A) at amino acid position 691 to be replaced by a valine (V). 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

0.29

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.22

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.17

.;T;.;.;T

Eigen

Uncertain

0.64

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.88

D;D;D;D;.

M_CAP

Benign

0.049

MetaRNN

Benign

0.27

T;T;T;T;T

MetaSVM

Uncertain

0.041

MutationAssessor

Uncertain

2.3

M;M;.;.;M

PrimateAI

Benign

0.47

PROVEAN

Benign

-2.1

N;N;N;N;N

REVEL

Uncertain

0.47

Sift

Benign

0.057

T;T;T;T;T

Sift4G

Uncertain

0.023

D;D;D;D;D

Polyphen

1.0

D;D;.;.;D

Vest4

0.18

MutPred

0.51

Gain of methylation at K690 (P = 0.0485);Gain of methylation at K690 (P = 0.0485);.;.;Gain of methylation at K690 (P = 0.0485);

MVP

0.92

MPC

0.30

ClinPred

0.42

GERP RS

5.2

Varity_R

0.18

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