8-6499929-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_024596.5(MCPH1):c.2214C>T(p.Pro738Pro) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000242 in 1,613,056 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_024596.5 splice_region, synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MCPH1 | ENST00000344683.10 | c.2214C>T | p.Pro738Pro | splice_region_variant, synonymous_variant | 12/14 | 1 | NM_024596.5 | ENSP00000342924.5 | ||
ANGPT2 | ENST00000629816 | c.*3172G>A | 3_prime_UTR_variant | 9/9 | 1 | NM_001118887.2 | ENSP00000486858.2 |
Frequencies
GnomAD3 genomes AF: 0.0000723 AC: 11AN: 152124Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000441 AC: 11AN: 249550Hom.: 0 AF XY: 0.0000443 AC XY: 6AN XY: 135392
GnomAD4 exome AF: 0.0000171 AC: 25AN: 1460814Hom.: 0 Cov.: 30 AF XY: 0.0000165 AC XY: 12AN XY: 726790
GnomAD4 genome AF: 0.0000920 AC: 14AN: 152242Hom.: 1 Cov.: 33 AF XY: 0.000121 AC XY: 9AN XY: 74464
ClinVar
Submissions by phenotype
Microcephaly 1, primary, autosomal recessive Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Mar 04, 2013 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 08, 2022 | Occurs in the last base pair of the exon Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at