4-78464515-C-CGG
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_025074.7(FRAS1):c.6963_6964dup(p.Val2322GlyfsTer6) variant causes a frameshift change. The variant allele was found at a frequency of 0.0000235 in 1,613,778 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. R2321R) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_025074.7 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FRAS1 | NM_025074.7 | c.6963_6964dup | p.Val2322GlyfsTer6 | frameshift_variant | 49/74 | ENST00000512123.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FRAS1 | ENST00000512123.4 | c.6963_6964dup | p.Val2322GlyfsTer6 | frameshift_variant | 49/74 | 5 | NM_025074.7 | P1 | |
FRAS1 | ENST00000682513.1 | c.6963_6964dup | p.Val2322GlyfsTer6 | frameshift_variant | 49/64 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152178Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000402 AC: 1AN: 248858Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 134972
GnomAD4 exome AF: 0.0000226 AC: 33AN: 1461600Hom.: 0 Cov.: 32 AF XY: 0.0000261 AC XY: 19AN XY: 727096
GnomAD4 genome AF: 0.0000329 AC: 5AN: 152178Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74350
ClinVar
Submissions by phenotype
not provided Pathogenic:3
Pathogenic, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2023 | FRAS1: PVS1, PM2 - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | This sequence change creates a premature translational stop signal (p.Val2322Glyfs*6) in the FRAS1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in FRAS1 are known to be pathogenic (PMID: 12766769, 18671281). This variant is present in population databases (rs730882179, gnomAD 0.004%). This premature translational stop signal has been observed in individual(s) with clinical features of FRAS1-related conditions (PMID: 16894541, 31999076). This variant is also known as 6992insGG. ClinVar contains an entry for this variant (Variation ID: 2815). For these reasons, this variant has been classified as Pathogenic. - |
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Jun 30, 2021 | Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 32488952, 16894541, 31999076) - |
Fraser syndrome 1 Pathogenic:3
Pathogenic, no assertion criteria provided | literature only | OMIM | Sep 15, 2006 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Sep 17, 2021 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Nov 19, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at