chr8-98027547-G-A

Position:

chr8-98027547-G-A

Variant summary

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

The ENST00000254898.7(MATN2):c.2074G>A(p.Ala692Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000421 in 1,613,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

MATN2
ENST00000254898.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.44

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=0.056629658).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MATN2	NM_002380.5 linkuse as main transcript	c.2074G>A	p.Ala692Thr	missense_variant	14/19	ENST00000254898.7	NP_002371.3
MATN2	NM_030583.4 linkuse as main transcript	c.2074G>A	p.Ala692Thr	missense_variant	14/19		NP_085072.2
MATN2	NM_001317748.2 linkuse as main transcript	c.1951G>A	p.Ala651Thr	missense_variant	13/18		NP_001304677.1
MATN2	XM_005250920.3 linkuse as main transcript	c.1943-2915G>A		intron_variant			XP_005250977.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MATN2	ENST00000254898.7 linkuse as main transcript	c.2074G>A	p.Ala692Thr	missense_variant	14/19	1	NM_002380.5	ENSP00000254898	P4	O00339-1

Frequencies

GnomAD3 genomes

AF:

0.000197

AC:

AN:

152054

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00157

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000522

AC:

AN:

249208

Hom.:

AF XY:

0.0000444

AC XY:

AN XY:

135192

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000261

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000556

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.0000260

AC:

AN:

1461698

Hom.:

Cov.:

AF XY:

0.0000248

AC XY:

AN XY:

727132

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000268

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000162

Gnomad4 OTH exome

AF:

0.0000663

GnomAD4 genome

AF:

0.000197

AC:

AN:

152172

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00157

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000181

ExAC

AF:

0.0000331

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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 26, 2023

The c.2074G>A (p.A692T) alteration is located in exon 14 (coding exon 13) of the MATN2 gene. This alteration results from a G to A substitution at nucleotide position 2074, causing the alanine (A) at amino acid position 692 to be replaced by a threonine (T). 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

-0.25

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.069

.;T;.;.;T

Eigen

Benign

0.037

Eigen_PC

Benign

0.18

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.91

D;D;D;D;.

M_CAP

Benign

0.023

MetaRNN

Benign

0.057

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.2

N;N;.;.;N

MutationTaster

Benign

0.99

D;D;D;D;D

PrimateAI

Benign

0.40

PROVEAN

Benign

1.1

N;N;N;N;N

REVEL

Uncertain

0.39

Sift

Benign

1.0

T;T;T;T;T

Sift4G

Benign

0.89

T;T;T;T;T

Polyphen

0.98

D;D;.;.;D

Vest4

0.11

MVP

0.91

MPC

0.51

ClinPred

0.22

GERP RS

5.2

Varity_R

0.11

gMVP

0.41

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