NM_001033855.3:c.512C>G
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BS2_SupportingBA1
This summary comes from the ClinGen Evidence Repository: The NM_001033855.3:c.512C>G variant in DCLRE1C is a missense variant predicted to cause the substitution of proline by arginine at amino acid 171 (p.Pro171Arg). This variant has an allele frequency of 0.19422 in the East Asian population in gnomAD, which is above the threshold for BA1 set by the ClinGen SCID VCEP for DCLRE1C (>0.00346). In addition, this variant is present 1394 adult homozygous individuals in gnomADv2.1.1 (distributed in all gnomAD populations)(BS2_Supporting). In summary, this variant meets the criteria to be classified as Benign for autosomal recessive SCID based on the ACMG criteria applied: BA1 and BS2_Supporting, as specified by the ClinGen SCID VCEP (VCEP specifications version 1). LINK:https://erepo.genome.network/evrepo/ui/classification/CA213684/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
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0965 AC: 14670AN: 151980Hom.: 779 Cov.: 31
GnomAD3 exomes AF: 0.0903 AC: 22714AN: 251472Hom.: 1241 AF XY: 0.0866 AC XY: 11769AN XY: 135908
GnomAD4 exome AF: 0.0794 AC: 116032AN: 1460812Hom.: 5234 Cov.: 33 AF XY: 0.0786 AC XY: 57153AN XY: 726756
GnomAD4 genome AF: 0.0966 AC: 14689AN: 152098Hom.: 785 Cov.: 31 AF XY: 0.0958 AC XY: 7127AN XY: 74376
ClinVar
Submissions by phenotype
Severe combined immunodeficiency due to DCLRE1C deficiency Benign:5
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The NM_001033855.3:c.512C>G variant in DCLRE1C is a missense variant predicted to cause the substitution of proline by arginine at amino acid 171 (p.Pro171Arg). This variant has an allele frequency of 0.19422 in the East Asian population in gnomAD, which is above the threshold for BA1 set by the ClinGen SCID VCEP for DCLRE1C (>0.00346). In addition, this variant is present 1394 adult homozygous individuals in gnomADv2.1.1 (distributed in all gnomAD populations)(BS2_Supporting). In summary, this variant meets the criteria to be classified as Benign for autosomal recessive SCID based on the ACMG criteria applied: BA1 and BS2_Supporting, as specified by the ClinGen SCID VCEP (VCEP specifications version 1). -
not provided Benign:3
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This variant is associated with the following publications: (PMID: 25917813, 21664875, 23701501, 20674517) -
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Histiocytic medullary reticulosis Benign:2
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This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
not specified Benign:1
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Severe combined immunodeficiency disease Benign:1
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Severe combined immunodeficiency due to DCLRE1C deficiency;C2700553:Histiocytic medullary reticulosis Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at