1-179561279-G-GT
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_StrongBS2
The NM_014625.4(NPHS2):c.451+9dupA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00046 in 1,605,678 control chromosomes in the GnomAD database, including 9 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0021 ( 5 hom., cov: 32)
Exomes 𝑓: 0.00028 ( 4 hom. )
Consequence
NPHS2
NM_014625.4 intron
NM_014625.4 intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.873
Genes affected
NPHS2 (HGNC:13394): (NPHS2 stomatin family member, podocin) This gene encodes a protein that plays a role in the regulation of glomerular permeability. Mutations in this gene cause steroid-resistant nephrotic syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP6
Variant 1-179561279-G-GT is Benign according to our data. Variant chr1-179561279-G-GT is described in ClinVar as [Likely_benign]. Clinvar id is 260427.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
High Homozygotes in GnomAd4 at 5 AR gene
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00216 AC: 328AN: 152066Hom.: 5 Cov.: 32
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GnomAD3 exomes AF: 0.000621 AC: 156AN: 251324Hom.: 0 AF XY: 0.000523 AC XY: 71AN XY: 135826
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GnomAD4 exome AF: 0.000283 AC: 412AN: 1453494Hom.: 4 Cov.: 29 AF XY: 0.000238 AC XY: 172AN XY: 723778
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GnomAD4 genome AF: 0.00215 AC: 327AN: 152184Hom.: 5 Cov.: 32 AF XY: 0.00200 AC XY: 149AN XY: 74426
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Dec 20, 2024 | Variant summary: NPHS2 c.451+9dupA alters a non-conserved nucleotide located at a position not widely known to affect splicing. Consensus agreement among computation tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00062 in 251324 control chromosomes, predominantly at a frequency of 0.0078 within the African or African-American subpopulation in the gnomAD database. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 4.41 fold of the estimated maximal expected allele frequency for a pathogenic variant in NPHS2 causing Nephrotic Syndrome, Type 2 phenotype (0.0018). To our knowledge, no occurrence of c.451+9dupA in individuals affected with Nephrotic Syndrome, Type 2 and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 260427). Based on the evidence outlined above, the variant was classified as benign. - |
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Dec 02, 2016 | - - |
Nephrotic syndrome, type 2 Benign:2
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Apr 11, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Sep 28, 2021 | - - |
Kidney disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Dec 08, 2021 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 24, 2024 | - - |
Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at