rs786203558
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PM4_Supporting
The NM_001042492.3(NF1):c.7057_7059del(p.Asp2353del) variant causes a inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,840 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. D2353D) has been classified as Likely benign.
Frequency
Consequence
NM_001042492.3 inframe_deletion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NF1 | NM_001042492.3 | c.7057_7059del | p.Asp2353del | inframe_deletion | 47/58 | ENST00000358273.9 | |
NF1 | NM_000267.3 | c.6994_6996del | p.Asp2332del | inframe_deletion | 46/57 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NF1 | ENST00000358273.9 | c.7057_7059del | p.Asp2353del | inframe_deletion | 47/58 | 1 | NM_001042492.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461840Hom.: 0 AF XY: 0.00000138 AC XY: 1AN XY: 727224
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Neurofibromatosis, type 1 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 19, 2024 | This variant, c.6994_6996del, results in the deletion of 1 amino acid(s) of the NF1 protein (p.Asp2332del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with NF1-related conditions. ClinVar contains an entry for this variant (Variation ID: 187215). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Mar 15, 2022 | - - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 20, 2014 | The c.7057_7059delGAC variant (also known as p.D2353del) is located in coding exon 47 of the NF1 gene. This variant results from an in-frame deletion of 3 nucleotidesat positions 7057 to 7059, causing the removal of a highly-conserved aspartic acid residue at codon 2353. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.007% (greater than 30000 alleles tested) in our clinical cohort.Since supporting evidence is limited at this time, the clinical significance of c.7057_7059delGAC remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at