chr8-98009781-C-A

Position:

• chr8-98009781-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002380.5(MATN2):​c.1573+2180C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.758 in 151,996 control chromosomes in the GnomAD database, including 43,970 homozygotes. 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 0.76 (43970 hom., cov: 31)
• Consequence: MATN2 NM_002380.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.143

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.791 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MATN2	NM_002380.5	c.1573+2180C>A		intron_variant		ENST00000254898.7	NP_002371.3
MATN2	NM_030583.4	c.1573+2180C>A		intron_variant			NP_085072.2
MATN2	NM_001317748.2	c.1450+2180C>A		intron_variant			NP_001304677.1
MATN2	XM_005250920.3	c.1573+2180C>A		intron_variant			XP_005250977.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MATN2	ENST00000254898.7	c.1573+2180C>A		intron_variant		1	NM_002380.5	ENSP00000254898.6
MATN2	ENST00000520016.5	c.1573+2180C>A		intron_variant		1		ENSP00000430487.1
MATN2	ENST00000521689.5	c.1573+2180C>A		intron_variant		1		ENSP00000429977.1
MATN2	ENST00000524308.5	c.1450+2180C>A		intron_variant		1		ENSP00000430221.1
MATN2	ENST00000518154.5	c.919+2180C>A		intron_variant		1		ENSP00000429622.1
MATN2	ENST00000522025.6	c.721+2180C>A		intron_variant		5		ENSP00000429010.1
MATN2	ENST00000521952.5	n.121+2180C>A		intron_variant		5		ENSP00000429256.1

Frequencies

GnomAD3 genomes AF: 0.758 AC: 115178 AN: 151880 Hom.: 43945 Cov.: 31

Gnomad AFR AF: 0.798

Gnomad AMI AF: 0.789

Gnomad AMR AF: 0.649

Gnomad ASJ AF: 0.812

Gnomad EAS AF: 0.706

Gnomad SAS AF: 0.646

Gnomad FIN AF: 0.717

Gnomad MID AF: 0.873

Gnomad NFE AF: 0.773

Gnomad OTH AF: 0.786

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.758 AC: 115248 AN: 151996 Hom.: 43970 Cov.: 31 AF XY: 0.752 AC XY: 55841 AN XY: 74282

Gnomad4 AFR AF: 0.798

Gnomad4 AMR AF: 0.648

Gnomad4 ASJ AF: 0.812

Gnomad4 EAS AF: 0.706

Gnomad4 SAS AF: 0.645

Gnomad4 FIN AF: 0.717

Gnomad4 NFE AF: 0.773

Gnomad4 OTH AF: 0.783

Alfa AF: 0.764 Hom.: 54978

Bravo AF: 0.759

Asia WGS AF: 0.661 AC: 2300 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.70
DANN	Benign	0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

Other links and lift over

dbSNP: rs2444896; hg19: chr8-99022009;