chr14-105643209-A-AC
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PVS1_StrongPP5
The ENST00000641095.1(IGHG2):c.973+1_973+2insG variant causes a splice donor change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: 𝑓 0.000098 ( 0 hom., cov: 15)
Exomes 𝑓: 0.00015 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
IGHG2
ENST00000641095.1 splice_donor
ENST00000641095.1 splice_donor
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.89
Genes affected
IGHG2 (HGNC:5526): (immunoglobulin heavy constant gamma 2 (G2m marker)) Predicted to enable antigen binding activity and immunoglobulin receptor binding activity. Predicted to be involved in several processes, including activation of immune response; defense response to other organism; and phagocytosis. Located in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 5 ACMG points.
PVS1
?
Splicing variant, NOT destroyed by nmd, known LOF gene, truncates exone, which is 0.26430976 fraction of the gene. Cryptic splice site detected, with MaxEntScore 4.5, offset of 1, new splice context is: gggGTaaat. Cryptic site results in frameshift change. If cryptic site found is not functional and variant results in exon loss, it results in inframe change.
PP5
?
Variant 14-105643209-A-AC is Pathogenic according to our data. Variant chr14-105643209-A-AC is described in ClinVar as [Pathogenic]. Clinvar id is 14808.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IGHG2 | ENST00000641095.1 | c.973+1_973+2insG | splice_donor_variant | P5 | |||||
IGHG2 | ENST00000390545.3 | c.974_975insG | p.Lys326Ter | frameshift_variant | 4/4 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000983 AC: 12AN: 122124Hom.: 0 Cov.: 15
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GnomAD3 exomes AF: 0.0000670 AC: 16AN: 238856Hom.: 1 AF XY: 0.0000768 AC XY: 10AN XY: 130224
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000150 AC: 93AN: 621598Hom.: 0 Cov.: 0 AF XY: 0.000133 AC XY: 45AN XY: 338010
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GnomAD4 genome ? AF: 0.0000982 AC: 12AN: 122228Hom.: 0 Cov.: 15 AF XY: 0.000103 AC XY: 6AN XY: 58230
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Decreased circulating IgG2 level Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Feb 01, 1998 | - - |
Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at