8-98027693-C-A

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002380.5(MATN2):c.2220C>A(p.His740Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000316 in 1,613,820 control chromosomes in the GnomAD database, including 1 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000034 ( 1 hom. )

Consequence

MATN2
NM_002380.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.01

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09146872).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MATN2	NM_002380.5 link	c.2220C>A	p.His740Gln	missense_variant	Exon 14 of 19	ENST00000254898.7	NP_002371.3	O00339-1A0A140VKH7Q8N2G3
MATN2	NM_030583.4 link	c.2220C>A	p.His740Gln	missense_variant	Exon 14 of 19		NP_085072.2	O00339-2Q8N2G3
MATN2	NM_001317748.2 link	c.2097C>A	p.His699Gln	missense_variant	Exon 13 of 18		NP_001304677.1	O00339-3Q8N2G3
MATN2	XM_005250920.3 link	c.1943-2769C>A		intron_variant	Intron 13 of 17		XP_005250977.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MATN2	ENST00000254898.7 link	c.2220C>A	p.His740Gln	missense_variant	Exon 14 of 19	1	NM_002380.5	ENSP00000254898.6	O00339-1
MATN2	ENST00000520016.5 link	c.2220C>A	p.His740Gln	missense_variant	Exon 13 of 18	1		ENSP00000430487.1	O00339-1
MATN2	ENST00000521689.5 link	c.2220C>A	p.His740Gln	missense_variant	Exon 14 of 19	1		ENSP00000429977.1	O00339-2
MATN2	ENST00000524308.5 link	c.2097C>A	p.His699Gln	missense_variant	Exon 13 of 18	1		ENSP00000430221.1	O00339-3
MATN2	ENST00000518154.5 link	c.1566C>A	p.His522Gln	missense_variant	Exon 11 of 16	1		ENSP00000429622.1	H0YBJ4
MATN2	ENST00000522025.6 link	c.1368C>A	p.His456Gln	missense_variant	Exon 13 of 18	5		ENSP00000429010.1	O00339-4
MATN2	ENST00000521952.5 link	n.*25-2769C>A		intron_variant	Intron 4 of 8	5		ENSP00000429256.1	H0YBD5

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000764

AC:

AN:

248658

Hom.:

AF XY:

0.000126

AC XY:

AN XY:

134954

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000621

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000342

AC:

AN:

1461672

Hom.:

Cov.:

AF XY:

0.0000591

AC XY:

AN XY:

727116

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152148

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000745

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 28, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2220C>A (p.H740Q) alteration is located in exon 14 (coding exon 13) of the MATN2 gene. This alteration results from a C to A substitution at nucleotide position 2220, causing the histidine (H) at amino acid position 740 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

0.20

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.19

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.28

.;T;.;.;T

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.16

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.74

T;T;T;T;.

M_CAP

Benign

0.015

MetaRNN

Benign

0.091

T;T;T;T;T

MetaSVM

Benign

-0.64

MutationAssessor

Benign

1.8

L;L;.;.;L

PrimateAI

Uncertain

0.68

PROVEAN

Uncertain

-2.5

D;N;N;D;N

REVEL

Uncertain

0.38

Sift

Benign

0.11

T;T;T;T;T

Sift4G

Benign

0.22

T;T;T;T;T

Polyphen

0.0040

B;B;.;.;B

Vest4

0.12

MutPred

0.64

Loss of ubiquitination at K739 (P = 0.0768);Loss of ubiquitination at K739 (P = 0.0768);.;.;Loss of ubiquitination at K739 (P = 0.0768);

MVP

0.84

MPC

0.22

ClinPred

0.11

GERP RS

1.2

Varity_R

0.15

gMVP

0.64

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