rs2290470

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr8-97931218-T-G
• chr8-97931218-T-A
• chr8-97931218-T-C

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_002380.5(MATN2):​c.408T>G​(p.Thr136Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00102 in 1,613,070 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0054 (7 hom., cov: 32)
  • Exomes 𝑓: 0.00056 (7 hom.)
• Consequence: MATN2 NM_002380.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 8-97931218-T-G is Benign according to our data. Variant chr8-97931218-T-G is described in ClinVar as Benign. ClinVar VariationId is 778944.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-6.57 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00537 (817/152076) while in subpopulation AFR AF = 0.0185 (769/41498). AF 95% confidence interval is 0.0174. There are 7 homozygotes in GnomAd4. There are 390 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 7 AR gene

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>G	p.Thr136Thr	synonymous	Exon 3 of 19	NP_002371.3
	MATN2	NM_030583.4		c.408T>G	p.Thr136Thr	synonymous	Exon 3 of 19	NP_085072.2	O00339-2
	MATN2	NM_001317748.2		c.408T>G	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>G	p.Thr136Thr	synonymous	Exon 3 of 19	ENSP00000254898.6	O00339-1
	MATN2	ENST00000520016.5	TSL:1	c.408T>G	p.Thr136Thr	synonymous	Exon 2 of 18	ENSP00000430487.1	O00339-1
	MATN2	ENST00000521689.5	TSL:1	c.408T>G	p.Thr136Thr	synonymous	Exon 3 of 19	ENSP00000429977.1	O00339-2

Frequencies

GnomAD3 genomes AF: 0.00536 AC: 815 AN: 151956 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.0185

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00242

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: 0.0000588

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.00137 AC: 341 AN: 248062 AF XY: 0.000937

Gnomad AFR exome AF: 0.0197

Gnomad AMR exome AF: 0.000901

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000891

Gnomad OTH exome AF: 0.000830

GnomAD4 exome AF: 0.000562 AC: 821 AN: 1460994 Hom.: 7 Cov.: 50 AF XY: 0.000453 AC XY: 329 AN XY: 726668

African (AFR) AF: 0.0198 AC: 664 AN: 33472

American (AMR) AF: 0.00105 AC: 47 AN: 44656

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39648

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53366

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5766

European-Non Finnish (NFE) AF: 0.0000180 AC: 20 AN: 1111368

Other (OTH) AF: 0.00142 AC: 86 AN: 60354

GnomAD4 genome AF: 0.00537 AC: 817 AN: 152076 Hom.: 7 Cov.: 32 AF XY: 0.00525 AC XY: 390 AN XY: 74338

African (AFR) AF: 0.0185 AC: 769 AN: 41498

American (AMR) AF: 0.00242 AC: 37 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5160

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10544

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000589 AC: 4 AN: 67968

Other (OTH) AF: 0.00284 AC: 6 AN: 2110

Alfa AF: 0.0000258 Hom.: 10992

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.092
DANN	Benign	0.60
PhyloP100		-6.6
PromoterAI		-0.00060	Neutral
Mutation Taster		=98/2	polymorphism

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;