rs61747727
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM1BP4_StrongBP6BA1
The NM_014625.4(NPHS2):c.725C>T(p.Ala242Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00373 in 1,613,414 control chromosomes in the GnomAD database, including 209 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A242T) has been classified as Uncertain significance.
Frequency
Consequence
NM_014625.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NPHS2 | NM_014625.4 | c.725C>T | p.Ala242Val | missense_variant | 5/8 | ENST00000367615.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NPHS2 | ENST00000367615.9 | c.725C>T | p.Ala242Val | missense_variant | 5/8 | 1 | NM_014625.4 | P1 | |
NPHS2 | ENST00000367616.4 | c.535-2509C>T | intron_variant | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0204 AC: 3109AN: 152196Hom.: 109 Cov.: 32
GnomAD3 exomes AF: 0.00536 AC: 1342AN: 250452Hom.: 48 AF XY: 0.00392 AC XY: 531AN XY: 135364
GnomAD4 exome AF: 0.00199 AC: 2906AN: 1461100Hom.: 99 Cov.: 31 AF XY: 0.00169 AC XY: 1225AN XY: 726880
GnomAD4 genome ? AF: 0.0204 AC: 3110AN: 152314Hom.: 110 Cov.: 32 AF XY: 0.0201 AC XY: 1494AN XY: 74474
ClinVar
Submissions by phenotype
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 19, 2020 | This variant is associated with the following publications: (PMID: 32691731, 30450462, 26211502, 12707396, 20981092) - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jun 19, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Nephrotic syndrome, type 2 Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Institute of Human Genetics, University of Leipzig Medical Center | Jan 01, 2019 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 28, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. - |
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Nov 02, 2018 | Variant summary: NPHS2 c.725C>T (p.Ala242Val) results in a non-conservative amino acid change located in the Band 7 domain of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0069 in 276216 control chromosomes, predominantly within the African subpopulation at a frequency of 0.073 in the gnomAD database, including 67 homozygotes. The observed variant frequency within African control individuals in the gnomAD database is approximately 41-fold above the estimated maximal expected allele frequency for a pathogenic variant in NPHS2 causing Nephrotic Syndrome, Type 2 phenotype (0.0018), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African origin. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as benign. Based on the evidence outlined above, the variant was classified as benign. - |
Steroid-resistant nephrotic syndrome Benign:1
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Focal segmental glomerulosclerosis Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Mar 14, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at