chr2-19994275-G-C

Variant names:

• chr2-19994275-G-C
• rs3820949
• NM_002381.5:c.1405+24C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002381.5(MATN3):​c.1405+24C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.444 in 1,522,864 control chromosomes in the GnomAD database, including 153,781 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.46 (16044 hom., cov: 33)
  • Exomes 𝑓: 0.44 (137737 hom.)
• Consequence: MATN3 NM_002381.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.171

Genes affected

MATN3 (HGNC:6909): (matrilin 3) This gene encodes a member of 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 two von Willebrand factor A domains; it is present in the cartilage extracellular matrix and has a role in the development and homeostasis of cartilage and bone. Mutations in this gene result in multiple epiphyseal dysplasia. [provided by RefSeq, Jul 2008]

WDR35-DT (HGNC:55818): (WDR35 divergent transcript)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 2-19994275-G-C is Benign according to our data. Variant chr2-19994275-G-C is described in ClinVar as [Benign]. Clinvar id is 258646.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.62 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MATN3	NM_002381.5	c.1405+24C>G		intron_variant	Intron 7 of 7	ENST00000407540.8	NP_002372.1
WDR35-DT	NR_110235.1	n.291+3781G>C		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MATN3	ENST00000407540.8	c.1405+24C>G		intron_variant	Intron 7 of 7	1	NM_002381.5	ENSP00000383894.3

Frequencies

GnomAD3 genomes AF: 0.456 AC: 69280 AN: 151898 Hom.: 16020 Cov.: 33

Gnomad AFR AF: 0.469

Gnomad AMI AF: 0.533

Gnomad AMR AF: 0.491

Gnomad ASJ AF: 0.408

Gnomad EAS AF: 0.639

Gnomad SAS AF: 0.589

Gnomad FIN AF: 0.431

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.422

Gnomad OTH AF: 0.466

GnomAD2 exomes AF: 0.473 AC: 108917 AN: 230198 AF XY: 0.476

Gnomad AFR exome AF: 0.468

Gnomad AMR exome AF: 0.493

Gnomad ASJ exome AF: 0.416

Gnomad EAS exome AF: 0.635

Gnomad FIN exome AF: 0.436

Gnomad NFE exome AF: 0.420

Gnomad OTH exome AF: 0.469

GnomAD4 exome AF: 0.443 AC: 607377 AN: 1370848 Hom.: 137737 Cov.: 20 AF XY: 0.447 AC XY: 306248 AN XY: 685226

Gnomad4 AFR exome AF: 0.473 AC: 15069 AN: 31846

Gnomad4 AMR exome AF: 0.486 AC: 20816 AN: 42796

Gnomad4 ASJ exome AF: 0.422 AC: 10675 AN: 25280

Gnomad4 EAS exome AF: 0.698 AC: 27234 AN: 39028

Gnomad4 SAS exome AF: 0.591 AC: 48793 AN: 82516

Gnomad4 FIN exome AF: 0.431 AC: 22676 AN: 52672

Gnomad4 NFE exome AF: 0.419 AC: 433611 AN: 1033718

Gnomad4 Remaining exome AF: 0.448 AC: 25691 AN: 57362

GnomAD4 genome AF: 0.456 AC: 69355 AN: 152016 Hom.: 16044 Cov.: 33 AF XY: 0.461 AC XY: 34282 AN XY: 74312

Gnomad4 AFR AF: 0.469 AC: 0.469192 AN: 0.469192

Gnomad4 AMR AF: 0.492 AC: 0.491813 AN: 0.491813

Gnomad4 ASJ AF: 0.408 AC: 0.408357 AN: 0.408357

Gnomad4 EAS AF: 0.638 AC: 0.638331 AN: 0.638331

Gnomad4 SAS AF: 0.587 AC: 0.58749 AN: 0.58749

Gnomad4 FIN AF: 0.431 AC: 0.430966 AN: 0.430966

Gnomad4 NFE AF: 0.422 AC: 0.422189 AN: 0.422189

Gnomad4 OTH AF: 0.473 AC: 0.472909 AN: 0.472909

Alfa AF: 0.437 Hom.: 2674

Bravo AF: 0.456

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	14
DANN	Benign	0.51
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3820949; hg19: chr2-20194036; COSMIC: COSV55606248; COSMIC: COSV55606248;