8-98033655-G-C

Position:

chr8-98033655-G-C

Variant summary

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

The ENST00000254898.7(MATN2):c.2811G>C(p.Gln937His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000395 in 1,587,982 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00035 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00040 ( 1 hom. )

Consequence

MATN2
ENST00000254898.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.903

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=0.05978644).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MATN2	NM_002380.5 linkuse as main transcript	c.2811G>C	p.Gln937His	missense_variant	18/19	ENST00000254898.7	NP_002371.3
MATN2	NM_030583.4 linkuse as main transcript	c.2754G>C	p.Gln918His	missense_variant	18/19		NP_085072.2
MATN2	NM_001317748.2 linkuse as main transcript	c.2688G>C	p.Gln896His	missense_variant	17/18		NP_001304677.1
MATN2	XM_005250920.3 linkuse as main transcript	c.2397G>C	p.Gln799His	missense_variant	17/18		XP_005250977.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MATN2	ENST00000254898.7 linkuse as main transcript	c.2811G>C	p.Gln937His	missense_variant	18/19	1	NM_002380.5	ENSP00000254898	P4	O00339-1

Frequencies

GnomAD3 genomes

AF:

0.000355

AC:

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000660

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000647

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000292

AC:

AN:

225776

Hom.:

AF XY:

0.000230

AC XY:

AN XY:

121488

show subpopulations

Gnomad AFR exome

AF:

0.0000733

Gnomad AMR exome

AF:

0.0000630

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000392

Gnomad NFE exome

AF:

0.000535

Gnomad OTH exome

AF:

0.000178

GnomAD4 exome

AF:

0.000399

AC:

573

AN:

1435678

Hom.:

Cov.:

AF XY:

0.000401

AC XY:

286

AN XY:

713490

show subpopulations

Gnomad4 AFR exome

AF:

0.0000605

Gnomad4 AMR exome

AF:

0.0000703

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000120

Gnomad4 FIN exome

AF:

0.000739

Gnomad4 NFE exome

AF:

0.000470

Gnomad4 OTH exome

AF:

0.000218

GnomAD4 genome

AF:

0.000355

AC:

AN:

152304

Hom.:

Cov.:

AF XY:

0.000389

AC XY:

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000660

Gnomad4 NFE

AF:

0.000647

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000420

Hom.:

Bravo

AF:

0.000291

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000610

AC:

ExAC

AF:

0.000257

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

Apr 06, 2024

The c.2811G>C (p.Q937H) alteration is located in exon 18 (coding exon 17) of the MATN2 gene. This alteration results from a G to C substitution at nucleotide position 2811, causing the glutamine (Q) at amino acid position 937 to be replaced by a histidine (H). 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

0.18

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

.;T;.;.;T

Eigen

Benign

0.011

Eigen_PC

Benign

0.036

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.88

D;D;D;D;.

M_CAP

Benign

0.022

MetaRNN

Benign

0.060

T;T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.7

.;L;.;.;L

MutationTaster

Benign

0.68

D;D;N;N;N

PrimateAI

Benign

0.39

PROVEAN

Benign

-2.2

N;N;N;N;N

REVEL

Benign

0.26

Sift

Uncertain

0.0070

D;D;D;D;D

Sift4G

Uncertain

0.055

T;T;T;D;T

Polyphen

0.97

D;D;.;.;D

Vest4

0.41

MutPred

0.52

.;Loss of MoRF binding (P = 0.0907);.;.;Loss of MoRF binding (P = 0.0907);

MVP

0.59

MPC

0.66

ClinPred

0.27

GERP RS

2.1

Varity_R

0.67

gMVP

0.55

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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