NM_002380.5:c.408T>C

Variant names:

• chr8-97931218-T-C
• rs2290470
• NM_002380.5:c.408T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_002380.5(MATN2):​c.408T>C​(p.Thr136Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.35 in 1,612,890 control chromosomes in the GnomAD database, including 104,347 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. Synonymous variant affecting the same amino acid position (i.e. T136T) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.33 (9170 hom., cov: 32)
  • Exomes 𝑓: 0.35 (95177 hom.)
• Consequence: MATN2 NM_002380.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -6.57
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP7: Synonymous conserved (PhyloP=-6.57 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.735 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002380.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MATN2	NM_002380.5	MANE Select	c.408T>C	p.Thr136Thr	synonymous	Exon 3 of 19	NP_002371.3
	MATN2	NM_030583.4		c.408T>C	p.Thr136Thr	synonymous	Exon 3 of 19	NP_085072.2	O00339-2
	MATN2	NM_001317748.2		c.408T>C	p.Thr136Thr	synonymous	Exon 3 of 18	NP_001304677.1	O00339-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MATN2	ENST00000254898.7	TSL:1 MANE Select	c.408T>C	p.Thr136Thr	synonymous	Exon 3 of 19	ENSP00000254898.6	O00339-1
	MATN2	ENST00000520016.5	TSL:1	c.408T>C	p.Thr136Thr	synonymous	Exon 2 of 18	ENSP00000430487.1	O00339-1
	MATN2	ENST00000521689.5	TSL:1	c.408T>C	p.Thr136Thr	synonymous	Exon 3 of 19	ENSP00000429977.1	O00339-2

Frequencies

GnomAD3 genomes AF: 0.331 AC: 50251 AN: 151872 Hom.: 9165 Cov.: 32

Gnomad AFR AF: 0.254

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.310

Gnomad EAS AF: 0.756

Gnomad SAS AF: 0.494

Gnomad FIN AF: 0.277

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.344

Gnomad OTH AF: 0.357

GnomAD2 exomes AF: 0.377 AC: 93577 AN: 248062 AF XY: 0.385

Gnomad AFR exome AF: 0.257

Gnomad AMR exome AF: 0.329

Gnomad ASJ exome AF: 0.298

Gnomad EAS exome AF: 0.768

Gnomad FIN exome AF: 0.282

Gnomad NFE exome AF: 0.344

Gnomad OTH exome AF: 0.351

GnomAD4 exome AF: 0.352 AC: 514402 AN: 1460898 Hom.: 95177 Cov.: 50 AF XY: 0.356 AC XY: 258666 AN XY: 726604

African (AFR) AF: 0.249 AC: 8342 AN: 33472

American (AMR) AF: 0.328 AC: 14635 AN: 44648

Ashkenazi Jewish (ASJ) AF: 0.299 AC: 7813 AN: 26130

East Asian (EAS) AF: 0.708 AC: 28088 AN: 39648

South Asian (SAS) AF: 0.479 AC: 41338 AN: 86228

European-Finnish (FIN) AF: 0.290 AC: 15459 AN: 53360

Middle Eastern (MID) AF: 0.400 AC: 2304 AN: 5766

European-Non Finnish (NFE) AF: 0.337 AC: 374178 AN: 1111292

Other (OTH) AF: 0.369 AC: 22245 AN: 60354

GnomAD4 genome AF: 0.331 AC: 50275 AN: 151992 Hom.: 9170 Cov.: 32 AF XY: 0.334 AC XY: 24808 AN XY: 74290

African (AFR) AF: 0.254 AC: 10523 AN: 41472

American (AMR) AF: 0.325 AC: 4973 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.310 AC: 1076 AN: 3472

East Asian (EAS) AF: 0.755 AC: 3895 AN: 5158

South Asian (SAS) AF: 0.495 AC: 2384 AN: 4816

European-Finnish (FIN) AF: 0.277 AC: 2918 AN: 10540

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.344 AC: 23404 AN: 67940

Other (OTH) AF: 0.363 AC: 766 AN: 2108

Alfa AF: 0.329 Hom.: 10992

Bravo AF: 0.334

EpiCase AF: 0.350

EpiControl AF: 0.356

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.10
DANN	Benign	0.64
PhyloP100		-6.6
PromoterAI		-0.0052	Neutral
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2290470; hg19: chr8-98943446; COSMIC: COSV54712869; COSMIC: COSV54712869;