rs141582110
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2
The NM_001271938.2(MEGF8):c.2299-15_2299-12del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00469 in 1,604,856 control chromosomes in the GnomAD database, including 46 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0032 ( 2 hom., cov: 32)
Exomes 𝑓: 0.0049 ( 44 hom. )
Consequence
MEGF8
NM_001271938.2 splice_polypyrimidine_tract, intron
NM_001271938.2 splice_polypyrimidine_tract, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.349
Genes affected
MEGF8 (HGNC:3233): (multiple EGF like domains 8) The protein encoded by this gene is a single-pass type I membrane protein of unknown function that contains several EGF-like domains, Kelch repeats, and PSI domains. Defects in this gene are a cause of Carpenter syndrome 2. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2012]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP6
?
Variant 19-42349479-ATCAC-A is Benign according to our data. Variant chr19-42349479-ATCAC-A is described in ClinVar as [Likely_benign]. Clinvar id is 446027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00317 (482/152060) while in subpopulation SAS AF= 0.0145 (70/4820). AF 95% confidence interval is 0.0118. There are 2 homozygotes in gnomad4. There are 258 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MEGF8 | NM_001271938.2 | c.2299-15_2299-12del | splice_polypyrimidine_tract_variant, intron_variant | ENST00000251268.11 | |||
MEGF8 | NM_001410.3 | c.2098-15_2098-12del | splice_polypyrimidine_tract_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MEGF8 | ENST00000251268.11 | c.2299-15_2299-12del | splice_polypyrimidine_tract_variant, intron_variant | 5 | NM_001271938.2 | A2 | |||
MEGF8 | ENST00000334370.8 | c.2098-15_2098-12del | splice_polypyrimidine_tract_variant, intron_variant | 1 | P2 | ||||
MEGF8 | ENST00000378073.5 | c.-4787-15_-4787-12del | splice_polypyrimidine_tract_variant, intron_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00318 AC: 483AN: 151944Hom.: 2 Cov.: 32
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GnomAD3 exomes AF: 0.00538 AC: 1296AN: 240788Hom.: 15 AF XY: 0.00591 AC XY: 772AN XY: 130726
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GnomAD4 exome AF: 0.00485 AC: 7050AN: 1452796Hom.: 44 AF XY: 0.00522 AC XY: 3766AN XY: 721830
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GnomAD4 genome ? AF: 0.00317 AC: 482AN: 152060Hom.: 2 Cov.: 32 AF XY: 0.00347 AC XY: 258AN XY: 74336
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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
Benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 29, 2019 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Apr 28, 2017 | - - |
MEGF8-related Carpenter syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Computational scores
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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