chr5-127339238-C-G
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001256545.2(MEGF10):c.218+17C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00347 in 1,569,170 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0025 ( 1 hom., cov: 32)
Exomes 𝑓: 0.0036 ( 18 hom. )
Consequence
MEGF10
NM_001256545.2 intron
NM_001256545.2 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.231
Genes affected
MEGF10 (HGNC:29634): (multiple EGF like domains 10) This gene encodes a member of the multiple epidermal growth factor-like domains protein family. The encoded protein plays a role in cell adhesion, motility and proliferation, and is a critical mediator of apoptotic cell phagocytosis as well as amyloid-beta peptide uptake in the brain. Expression of this gene may be associated with schizophrenia, and mutations in this gene are a cause of early-onset myopathy, areflexia, respiratory distress, and dysphagia (EMARDD) as well as congenital myopathy with minicores. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Apr 2012]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BP6
?
Variant 5-127339238-C-G is Benign according to our data. Variant chr5-127339238-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 262070.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00247 (376/152120) while in subpopulation NFE AF= 0.0038 (258/67984). AF 95% confidence interval is 0.00341. There are 1 homozygotes in gnomad4. There are 186 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAdExome at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MEGF10 | NM_001256545.2 | c.218+17C>G | intron_variant | ENST00000503335.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MEGF10 | ENST00000503335.7 | c.218+17C>G | intron_variant | 1 | NM_001256545.2 | P1 | |||
MEGF10 | ENST00000274473.6 | c.218+17C>G | intron_variant | 1 | P1 | ||||
MEGF10 | ENST00000418761.6 | c.218+17C>G | intron_variant | 1 | |||||
MEGF10 | ENST00000508365.5 | c.218+17C>G | intron_variant | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.00247 AC: 376AN: 152002Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.00232 AC: 575AN: 247516Hom.: 2 AF XY: 0.00224 AC XY: 300AN XY: 133704
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GnomAD4 exome AF: 0.00358 AC: 5069AN: 1417050Hom.: 18 Cov.: 23 AF XY: 0.00340 AC XY: 2405AN XY: 707404
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
MEGF10-related myopathy Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 21, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Centre for Mendelian Genomics, University Medical Centre Ljubljana | Oct 31, 2018 | This variant was classified as: Benign. The following ACMG criteria were applied in classifying this variant: BS1,BS2. - |
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 02, 2017 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
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