chr20-10648607-T-C
Variant summary
Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BS1_SupportingBS2
The NM_000214.3(JAG1):c.1511A>G(p.Asn504Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000242 in 1,614,168 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. N504N) has been classified as Likely benign.
Frequency
Consequence
NM_000214.3 missense
Scores
Clinical Significance
Conservation
Publications
- Alagille syndrome due to a JAG1 point mutationInheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia
- Charcot-Marie-Tooth disease, axonal, Type 2HHInheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
- tetralogy of fallotInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Our verdict: Likely_benign. The variant received -5 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152222Hom.: 0 Cov.: 33 show subpopulations
GnomAD2 exomes AF: 0.0000398 AC: 10AN: 251448 AF XY: 0.0000442 show subpopulations
GnomAD4 exome AF: 0.0000260 AC: 38AN: 1461828Hom.: 0 Cov.: 33 AF XY: 0.0000303 AC XY: 22AN XY: 727220 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.00000656 AC: 1AN: 152340Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74494 show subpopulations
ClinVar
Submissions by phenotype
Alagille syndrome due to a JAG1 point mutation Pathogenic:1Uncertain:1Benign:1
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Isolated Nonsyndromic Congenital Heart Disease Uncertain:1
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. -
not provided Uncertain:1
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Tetralogy of Fallot;C1866053:Deafness, congenital heart defects, and posterior embryotoxon;C1956125:Alagille syndrome due to a JAG1 point mutation;C5562003:Charcot-Marie-Tooth disease, axonal, Type 2HH Uncertain:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at