rs146796266
Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS1
The NM_001038603.3(MARVELD2):c.615C>T(p.Ala205=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000217 in 1,614,062 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0011 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00012 ( 2 hom. )
Consequence
MARVELD2
NM_001038603.3 synonymous
NM_001038603.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -5.18
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.59).
BP6
?
Variant 5-69420000-C-T is Benign according to our data. Variant chr5-69420000-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 43846.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-69420000-C-T is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=-5.18 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00115 (175/152174) while in subpopulation AFR AF= 0.0041 (170/41496). AF 95% confidence interval is 0.00359. There are 0 homozygotes in gnomad4. There are 72 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.615C>T | p.Ala205= | synonymous_variant | 2/7 | ENST00000325631.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MARVELD2 | ENST00000325631.10 | c.615C>T | p.Ala205= | synonymous_variant | 2/7 | 1 | NM_001038603.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00115 AC: 175AN: 152056Hom.: 0 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
175
AN:
152056
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000254 AC: 64AN: 251486Hom.: 0 AF XY: 0.000140 AC XY: 19AN XY: 135916
GnomAD3 exomes
AF:
AC:
64
AN:
251486
Hom.:
AF XY:
AC XY:
19
AN XY:
135916
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000120 AC: 175AN: 1461888Hom.: 2 Cov.: 35 AF XY: 0.000105 AC XY: 76AN XY: 727244
GnomAD4 exome
AF:
AC:
175
AN:
1461888
Hom.:
Cov.:
35
AF XY:
AC XY:
76
AN XY:
727244
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.00115 AC: 175AN: 152174Hom.: 0 Cov.: 32 AF XY: 0.000968 AC XY: 72AN XY: 74404
GnomAD4 genome
?
AF:
AC:
175
AN:
152174
Hom.:
Cov.:
32
AF XY:
AC XY:
72
AN XY:
74404
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 05, 2020 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 30, 2012 | Ala205Ala in Exon 02 of MARVELD2: This variant is not expected to have clinical significance because it does not alter an amino acid residue, is not located wit hin the splice consensus sequence, and has been identified in 0.4% (15/3738) of African American chromosomes from a broad population by the NHLBI Exome Sequenci ng Project (http://evs.gs.washington.edu/EVS; dbSNP rs146796266). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at