Genetic Variant NM_002380.5:c.2677C>A (chr8-98033137-C-A) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP7

The NM_002380.5(MATN2):c.2677C>A(p.Arg893Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,174 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 0.0000066 ( 0 hom., cov: 33)

Consequence

MATN2
NM_002380.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.486

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.23).

BP7

Synonymous conserved (PhyloP=0.486 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MATN2	NM_002380.5 link	c.2677C>A	p.Arg893Arg	synonymous_variant	Exon 17 of 19	ENST00000254898.7	NP_002371.3	O00339-1A0A140VKH7Q8N2G3
MATN2	NM_030583.4 link	c.2620C>A	p.Arg874Arg	synonymous_variant	Exon 17 of 19		NP_085072.2	O00339-2Q8N2G3
MATN2	NM_001317748.2 link	c.2554C>A	p.Arg852Arg	synonymous_variant	Exon 16 of 18		NP_001304677.1	O00339-3Q8N2G3
MATN2	XM_005250920.3 link	c.2263C>A	p.Arg755Arg	synonymous_variant	Exon 16 of 18		XP_005250977.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MATN2	ENST00000254898.7 link	c.2677C>A	p.Arg893Arg	synonymous_variant	Exon 17 of 19	1	NM_002380.5	ENSP00000254898.6	O00339-1
MATN2	ENST00000520016.5 link	c.2677C>A	p.Arg893Arg	synonymous_variant	Exon 16 of 18	1		ENSP00000430487.1	O00339-1
MATN2	ENST00000521689.5 link	c.2620C>A	p.Arg874Arg	synonymous_variant	Exon 17 of 19	1		ENSP00000429977.1	O00339-2
MATN2	ENST00000524308.5 link	c.2554C>A	p.Arg852Arg	synonymous_variant	Exon 16 of 18	1		ENSP00000430221.1	O00339-3
MATN2	ENST00000518154.5 link	c.1966C>A	p.Arg656Arg	synonymous_variant	Exon 14 of 16	1		ENSP00000429622.1	H0YBJ4
MATN2	ENST00000522025.6 link	c.1825C>A	p.Arg609Arg	synonymous_variant	Exon 16 of 18	5		ENSP00000429010.1	O00339-4
MATN2	ENST00000521952.5 link	n.*345C>A		non_coding_transcript_exon_variant	Exon 7 of 9	5		ENSP00000429256.1	H0YBD5
MATN2	ENST00000521952.5 link	n.*345C>A		3_prime_UTR_variant	Exon 7 of 9	5		ENSP00000429256.1	H0YBD5

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152174

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:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152174

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74348

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:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.23

CADD

Benign

7.9

DANN

Benign

0.82

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over