17-8006707-C-T
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BS2BP4BA1BP7
This summary comes from the ClinGen Evidence Repository: NM_000180.4(GUCY2D):c.1371C>T (p.Cys457=) is a synonymous variant in exon 4 of 20. This variant is present in gnomAD v.4.1.0 at a GrpMax allele frequency of 0.1129, with 5137 alleles/44460 total alleles and 134 homozygotes in the East Asian population, which is higher than the ClinGen LCA/eoRD VCEP BA1 threshold of >0.016. (BA1). This variant has been found in the homozygous state in 325 adult individuals in gnomAD which exceeds the LCA/eoRD VCEP threshold of ≥6 (gnomAD version 4.1.0; BS2). The computational predictor REVEL has no data as this is a synonymous variant. The splicing impact predictor SpliceAI gives a delta score of 0.02, which is below the ClinGen LCA/eoRD VCEP recommended threshold of <0.1 and does not predict an impact on splicing (BP4, BP7). In summary, this variant meets the criteria to be classified as Benign for GUCY2D-related recessive retinopathy based on the ACMG/AMP criteria applied, as specified by the ClinGen LCA/eoRD VCEP: BA1, BP4, BP7. (VCEP specifications version 1.0.0; date of approval 01/22/2025) LINK:https://erepo.genome.network/evrepo/ui/classification/CA202700/MONDO:0100453/167
Frequency
Consequence
NM_000180.4 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -14 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00492 AC: 749AN: 152216Hom.: 34 Cov.: 32
GnomAD3 exomes AF: 0.0101 AC: 2330AN: 229692Hom.: 128 AF XY: 0.00922 AC XY: 1154AN XY: 125164
GnomAD4 exome AF: 0.00388 AC: 5634AN: 1452372Hom.: 291 Cov.: 33 AF XY: 0.00380 AC XY: 2741AN XY: 721822
GnomAD4 genome AF: 0.00488 AC: 744AN: 152334Hom.: 34 Cov.: 32 AF XY: 0.00571 AC XY: 425AN XY: 74492
ClinVar
Submissions by phenotype
not specified Benign:2
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not provided Benign:2
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Cone-rod dystrophy 6;C2931258:Leber congenital amaurosis 1 Benign:1
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GUCY2D-related recessive retinopathy Benign:1
NM_000180.4(GUCY2D):c.1371C>T (p.Cys457=) is a synonymous variant in exon 4 of 20. This variant is present in gnomAD v.4.1.0 at a GrpMax allele frequency of 0.1129, with 5137 alleles/44460 total alleles and 134 homozygotes in the East Asian population, which is higher than the ClinGen LCA/eoRD VCEP BA1 threshold of >0.016. (BA1). This variant has been found in the homozygous state in 325 adult individuals in gnomAD which exceeds the LCA/eoRD VCEP threshold of ≥6 (gnomAD version 4.1.0; BS2). The computational predictor REVEL has no data as this is a synonymous variant. The splicing impact predictor SpliceAI gives a delta score of 0.02, which is below the ClinGen LCA/eoRD VCEP recommended threshold of <0.1 and does not predict an impact on splicing (BP4, BP7). In summary, this variant meets the criteria to be classified as Benign for GUCY2D-related recessive retinopathy based on the ACMG/AMP criteria applied, as specified by the ClinGen LCA/eoRD VCEP: BA1, BP4, BP7. (VCEP specifications version 1.0.0; date of approval 01/22/2025) -
Cone-rod dystrophy 6;C2931258:Leber congenital amaurosis 1;C4551884:Choroidal dystrophy, central areolar, 1;C5231408:Night blindness, congenital stationary, type1i Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at