rs201914751
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM2BP4_StrongBP6_Very_StrongBS1
The NM_001038603.3(MARVELD2):c.592G>A(p.Val198Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000966 in 1,614,192 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000094 ( 0 hom. )
Consequence
MARVELD2
NM_001038603.3 missense
NM_001038603.3 missense
Scores
4
9
Clinical Significance
Conservation
PhyloP100: 2.79
Genes affected
MARVELD2 (HGNC:26401): (MARVEL domain containing 2) The protein encoded by this gene is a membrane protein found at the tight junctions between epithelial cells. The encoded protein helps establish epithelial barriers such as those in the organ of Corti, where these barriers are required for normal hearing. Defects in this gene are a cause of deafness autosomal recessive type 49 (DFNB49). Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.012515366).
BP6
?
Variant 5-69419977-G-A is Benign according to our data. Variant chr5-69419977-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 163967.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000118 (18/152298) while in subpopulation EAS AF= 0.00347 (18/5190). AF 95% confidence interval is 0.00224. There are 0 homozygotes in gnomad4. There are 12 alleles in male gnomad4 subpopulation. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MARVELD2 | NM_001038603.3 | c.592G>A | p.Val198Met | missense_variant | 2/7 | ENST00000325631.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MARVELD2 | ENST00000325631.10 | c.592G>A | p.Val198Met | missense_variant | 2/7 | 1 | NM_001038603.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000118 AC: 18AN: 152180Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000282 AC: 71AN: 251484Hom.: 0 AF XY: 0.000235 AC XY: 32AN XY: 135916
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GnomAD4 exome AF: 0.0000944 AC: 138AN: 1461894Hom.: 0 Cov.: 35 AF XY: 0.0000935 AC XY: 68AN XY: 727248
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GnomAD4 genome ? AF: 0.000118 AC: 18AN: 152298Hom.: 0 Cov.: 32 AF XY: 0.000161 AC XY: 12AN XY: 74478
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ClinVar
Significance: Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Aug 15, 2022 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 19, 2021 | This variant is associated with the following publications: (PMID: 30406641) - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Nov 22, 2017 | p.Val198Met in exon 2 of MARVELD2: This variant is not expected to have clinical significance because it has been identified in 0.4% (72/18870) of East Asian ch romosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitu te.org; dbSNP rs201914751). ACMG/AMP Criteria applied: BS1. - |
MARVELD2-related condition Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 23, 2022 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
M;M;M;M;M;.;.
MutationTaster
Benign
N;N;N;N
PrimateAI
Uncertain
T
Polyphen
D;D;D;D;D;.;.
Vest4
0.33, 0.34, 0.32
MVP
0.59
MPC
0.34
ClinPred
T
GERP RS
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at