Submissions for variant NM_000123.4(ERCC5):c.1669G>A (p.Asp557Asn)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute	RCV002472088	SCV002768484	uncertain significance	Cerebrooculofacioskeletal syndrome 3	2022-02-02	criteria provided, single submitter	clinical testing	Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as VUS-3C. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with cerebrooculofacioskeletal syndrome 3 (MIM#616570) and group G xeroderma pigmentosum/Cockayne syndrome (MIM#278780). (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0200 - Variant is predicted to result in a missense amino acid change from aspartic acid to asparagine. (I) 0251 - This variant is heterozygous. (I) 0304 - Variant is present in gnomAD (v2) <0.01 for a recessive condition (9 heterozygotes, 0 homozygotes). (SP) 0309 - An alternative amino acid change at the same position has been observed in gnomAD (v2) (1 heterozygote, 0 homozygotes). (I) 0503 - Missense variant consistently predicted to be tolerated by multiple in silico tools or not conserved in placental mammals with a minor amino acid change. (SB) 0604 - Variant is not located in an established domain, motif, hotspot or informative constraint region. (I) 0705 - No comparable missense variants have previous evidence for pathogenicity. (I) 0807 - This variant has no previous evidence of pathogenicity. (I) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign
Ambry Genetics	RCV004067596	SCV003879044	uncertain significance	not specified	2023-01-31	criteria provided, single submitter	clinical testing	The c.3031G>A (p.D1011N) alteration is located in exon 16 (coding exon 16) of the BIVM-ERCC5 gene. This alteration results from a G to A substitution at nucleotide position 3031, causing the aspartic acid (D) at amino acid position 1011 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences	RCV004756400	SCV005347008	uncertain significance	ERCC5-related disorder	2024-05-10	no assertion criteria provided	clinical testing	The ERCC5 c.1669G>A variant is predicted to result in the amino acid substitution p.Asp557Asn. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.033% of alleles in individuals of East Asian descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.