chr8-98033138-G-A

Position:

chr8-98033138-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000254898.7(MATN2):c.2678G>A(p.Arg893Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00017 in 1,609,310 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R893W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00018 ( 1 hom. )

Consequence

MATN2
ENST00000254898.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.317

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 made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05833891).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MATN2	NM_002380.5 linkuse as main transcript	c.2678G>A	p.Arg893Gln	missense_variant	17/19	ENST00000254898.7	NP_002371.3
MATN2	NM_030583.4 linkuse as main transcript	c.2621G>A	p.Arg874Gln	missense_variant	17/19		NP_085072.2
MATN2	NM_001317748.2 linkuse as main transcript	c.2555G>A	p.Arg852Gln	missense_variant	16/18		NP_001304677.1
MATN2	XM_005250920.3 linkuse as main transcript	c.2264G>A	p.Arg755Gln	missense_variant	16/18		XP_005250977.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MATN2	ENST00000254898.7 linkuse as main transcript	c.2678G>A	p.Arg893Gln	missense_variant	17/19	1	NM_002380.5	ENSP00000254898	P4	O00339-1

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152084

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000725

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000191

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000824

AC:

AN:

242572

Hom.:

AF XY:

0.0000760

AC XY:

AN XY:

131582

show subpopulations

Gnomad AFR exome

AF:

0.000333

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:

0.000136

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000176

AC:

257

AN:

1457226

Hom.:

Cov.:

AF XY:

0.000182

AC XY:

132

AN XY:

724516

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.000222

Gnomad4 OTH exome

AF:

0.0000997

GnomAD4 genome

AF:

0.000105

AC:

AN:

152084

Hom.:

Cov.:

AF XY:

0.0000942

AC XY:

AN XY:

74278

show subpopulations

Gnomad4 AFR

AF:

0.0000725

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000203

Hom.:

Bravo

AF:

0.0000945

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000550

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000745

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 02, 2022

The c.2678G>A (p.R893Q) alteration is located in exon 17 (coding exon 16) of the MATN2 gene. This alteration results from a G to A substitution at nucleotide position 2678, causing the arginine (R) at amino acid position 893 to be replaced by a glutamine (Q). 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

0.065

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.016

.;T;.;.;T

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.65

FATHMM_MKL

Benign

0.50

LIST_S2

Benign

0.78

T;T;T;T;.

M_CAP

Benign

0.011

MetaRNN

Benign

0.058

T;T;T;T;T

MetaSVM

Benign

-0.86

MutationAssessor

Benign

0.0

.;N;.;.;N

MutationTaster

Benign

0.90

N;N;N;N;N

PrimateAI

Benign

0.18

PROVEAN

Benign

0.12

N;N;N;N;N

REVEL

Benign

0.13

Sift

Benign

0.14

T;T;T;T;T

Sift4G

Benign

0.30

T;T;T;T;T

Polyphen

0.0020

B;B;.;.;B

Vest4

0.12

MVP

0.70

MPC

0.22

ClinPred

0.036

GERP RS

0.26

Varity_R

0.036

gMVP

0.22

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