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GeneBe

8-97931218-T-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_002380.5(MATN2):c.408T>G(p.Thr136=) 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

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -6.57
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 8-97931218-T-G is Benign according to our data. Variant chr8-97931218-T-G is described in ClinVar as [Benign]. Clinvar id is 778944.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-6.57 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 7 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MATN2NM_002380.5 linkuse as main transcriptc.408T>G p.Thr136= synonymous_variant 3/19 ENST00000254898.7
MATN2NM_030583.4 linkuse as main transcriptc.408T>G p.Thr136= synonymous_variant 3/19
MATN2NM_001317748.2 linkuse as main transcriptc.408T>G p.Thr136= synonymous_variant 3/18
MATN2XM_005250920.3 linkuse as main transcriptc.408T>G p.Thr136= synonymous_variant 3/18

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MATN2ENST00000254898.7 linkuse as main transcriptc.408T>G p.Thr136= synonymous_variant 3/191 NM_002380.5 P4O00339-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00536
AC:
815
AN:
151956
Hom.:
7
Cov.:
32
show subpopulations
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
GnomAD3 exomes
AF:
0.00137
AC:
341
AN:
248062
Hom.:
2
AF XY:
0.000937
AC XY:
126
AN XY:
134504
show subpopulations
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 SAS 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
show subpopulations
Gnomad4 AFR exome
AF:
0.0198
Gnomad4 AMR exome
AF:
0.00105
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000180
Gnomad4 OTH exome
AF:
0.00142
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00537
AC:
817
AN:
152076
Hom.:
7
Cov.:
32
AF XY:
0.00525
AC XY:
390
AN XY:
74338
show subpopulations
Gnomad4 AFR
AF:
0.0185
Gnomad4 AMR
AF:
0.00242
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000589
Gnomad4 OTH
AF:
0.00284
Alfa
AF:
0.0000336
Hom.:
8504
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJul 06, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.90
Cadd
Benign
0.092
Dann
Benign
0.60

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2290470; hg19: chr8-98943446; API