rs113870881
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BA1BS2_Supporting
This summary comes from the ClinGen Evidence Repository: NM_001033855.3(DCLRE1C):c.1284A>C is a missense variant predicted to cause substitution of Lysine by Asparagine at amino acid 428 (p.Lys428Asn).The filtering allele frequency (the lower threshold of the 95% CI of 501/75018) of the c.1284A>C variant in DCLRE1C is 0.005719 for African/African American chromosomes by gnomAD v4, which is higher than the ClinGen SCID VCEP threshold (>0.00346) for BA1, and therefore meets this criterion (BA1). Additionally, 2 homozygous adults are reported in gnomAD v.4 in the same population. BS2_Supporting is Met.In summary, this variant meets the criteria to be classified as Benign for autosomal recessive severe combined immunodeficiency due to DCLRE1C deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen SCID-VCEP: BA1 and BS2_Supporting. (VCEP specifications version 1). LINK:https://erepo.genome.network/evrepo/ui/classification/CA5416508/MONDO:0011225/116
Frequency
Consequence
NM_001033855.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DCLRE1C | NM_001033855.3 | c.1284A>C | p.Lys428Asn | missense_variant | 14/14 | ENST00000378278.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DCLRE1C | ENST00000378278.7 | c.1284A>C | p.Lys428Asn | missense_variant | 14/14 | 1 | NM_001033855.3 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.00199 AC: 302AN: 152108Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000526 AC: 132AN: 251062Hom.: 0 AF XY: 0.000310 AC XY: 42AN XY: 135694
GnomAD4 exome AF: 0.000213 AC: 311AN: 1461828Hom.: 2 Cov.: 32 AF XY: 0.000166 AC XY: 121AN XY: 727214
GnomAD4 genome ? AF: 0.00201 AC: 306AN: 152226Hom.: 0 Cov.: 32 AF XY: 0.00193 AC XY: 144AN XY: 74430
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:2
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | May 01, 2016 | - - |
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Severe combined immunodeficiency due to DCLRE1C deficiency Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Benign, reviewed by expert panel | curation | ClinGen Severe Combined Immunodeficiency Variant Curation Expert Panel, ClinGen | Feb 05, 2024 | NM_001033855.3(DCLRE1C):c.1284A>C is a missense variant predicted to cause substitution of Lysine by Asparagine at amino acid 428 (p.Lys428Asn). The filtering allele frequency (the lower threshold of the 95% CI of 501/75018) of the c.1284A>C variant in DCLRE1C is 0.005719 for African/African American chromosomes by gnomAD v4, which is higher than the ClinGen SCID VCEP threshold (>0.00346) for BA1, and therefore meets this criterion (BA1). Additionally, 2 homozygous adults are reported in gnomAD v.4 in the same population. BS2_Supporting is Met. In summary, this variant meets the criteria to be classified as Benign for autosomal recessive severe combined immunodeficiency due to DCLRE1C deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen SCID-VCEP: BA1 and BS2_Supporting. (VCEP specifications version 1). - |
Likely benign, criteria provided, single submitter | clinical testing | Pars Genome Lab | May 18, 2021 | - - |
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 08, 2018 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Likely benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | May 19, 2016 | - - |
DCLRE1C-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 10, 2024 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at