rs1202258257
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1PM2PM5PP3_Moderate
The NM_000527.5(LDLR):āc.1895A>Gā(p.Asn632Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,784 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N632I) has been classified as Uncertain significance.
Frequency
Consequence
NM_000527.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LDLR | NM_000527.5 | c.1895A>G | p.Asn632Ser | missense_variant | 13/18 | ENST00000558518.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LDLR | ENST00000558518.6 | c.1895A>G | p.Asn632Ser | missense_variant | 13/18 | 1 | NM_000527.5 | P3 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461784Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1AN XY: 727210
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 24, 2021 | The p.N632S variant (also known as c.1895A>G), located in coding exon 13 of the LDLR gene, results from an A to G substitution at nucleotide position 1895. The asparagine at codon 632 is replaced by serine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at