14-104713555-G-A
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2
The NM_022489.4(INF2):c.2989G>A(p.Asp997Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000036 in 1,612,088 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. D997D) has been classified as Likely benign.
Frequency
Consequence
NM_022489.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
INF2 | NM_022489.4 | c.2989G>A | p.Asp997Asn | missense_variant | 20/23 | ENST00000392634.9 | |
INF2 | NM_001031714.4 | c.2989G>A | p.Asp997Asn | missense_variant | 20/22 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
INF2 | ENST00000392634.9 | c.2989G>A | p.Asp997Asn | missense_variant | 20/23 | 5 | NM_022489.4 | P4 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152170Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000610 AC: 15AN: 245794Hom.: 0 AF XY: 0.0000671 AC XY: 9AN XY: 134042
GnomAD4 exome AF: 0.0000370 AC: 54AN: 1459918Hom.: 0 Cov.: 35 AF XY: 0.0000344 AC XY: 25AN XY: 726164
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152170Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74334
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Feb 10, 2020 | The INF2 c.2989G>A; p.Asp997Asn variant (rs370719592), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 540041). This variant is found in the general population with an overall allele frequency of 0.01% (16/277120 alleles) in the Genome Aggregation Database. The aspartate at codon 997 is weakly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is tolerated. However, due to limited information, the clinical significance of the p.Asp997Asn variant is uncertain at this time. - |
Focal segmental glomerulosclerosis 5;C4302667:Charcot-Marie-Tooth disease dominant intermediate E Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 24, 2023 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 26, 2020 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at