rs372170366
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 1P and 7B. PP2BP4_ModerateBP6BS2
The NM_000393.5(COL5A2):c.4362T>A(p.Asn1454Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000335 in 1,613,848 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000393.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL5A2 | NM_000393.5 | c.4362T>A | p.Asn1454Lys | missense_variant | 54/54 | ENST00000374866.9 | |
COL5A2 | XM_011510573.4 | c.4224T>A | p.Asn1408Lys | missense_variant | 57/57 | ||
COL5A2 | XM_047443251.1 | c.4224T>A | p.Asn1408Lys | missense_variant | 59/59 | ||
COL5A2 | XM_047443252.1 | c.4224T>A | p.Asn1408Lys | missense_variant | 58/58 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL5A2 | ENST00000374866.9 | c.4362T>A | p.Asn1454Lys | missense_variant | 54/54 | 1 | NM_000393.5 | P1 | |
COL5A2 | ENST00000618828.1 | c.3201T>A | p.Asn1067Lys | missense_variant | 47/47 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.000171 AC: 26AN: 152200Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000638 AC: 16AN: 250944Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135634
GnomAD4 exome AF: 0.0000192 AC: 28AN: 1461648Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9AN XY: 727124
GnomAD4 genome ? AF: 0.000171 AC: 26AN: 152200Hom.: 0 Cov.: 32 AF XY: 0.000175 AC XY: 13AN XY: 74354
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | May 14, 2021 | Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant does not alter protein structure/function; Not located in the triple helical region, where the majority of pathogenic missense variants occur (Symoens et al., 2012; Stenson et al., 2014); Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 237777; Landrum et al., 2016) - |
Ehlers-Danlos syndrome, classic type, 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Sep 28, 2023 | - - |
Ehlers-Danlos syndrome, classic type Other:1
not provided, no classification provided | phenotyping only | GenomeConnect, ClinGen | - | GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at