rs387906870
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP5
The NM_004827.3(ABCG2):c.791_792del(p.Leu264HisfsTer14) variant causes a frameshift change. The variant allele was found at a frequency of 0.0000434 in 1,613,998 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000043 ( 0 hom. )
Consequence
ABCG2
NM_004827.3 frameshift
NM_004827.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 6.94
Genes affected
ABCG2 (HGNC:74): (ATP binding cassette subfamily G member 2 (JR blood group)) The membrane-associated protein encoded by this gene is included in the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the White subfamily. Alternatively referred to as a breast cancer resistance protein, this protein functions as a xenobiotic transporter which may play a major role in multi-drug resistance. It likely serves as a cellular defense mechanism in response to mitoxantrone and anthracycline exposure. Significant expression of this protein has been observed in the placenta, which may suggest a potential role for this molecule in placenta tissue. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 4-88118157-TAA-T is Pathogenic according to our data. Variant chr4-88118157-TAA-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 30388.We mark this variant Likely_pathogenic, oryginal submissions are: {Uncertain_significance=2, Pathogenic=1}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ABCG2 | NM_004827.3 | c.791_792del | p.Leu264HisfsTer14 | frameshift_variant | 7/16 | ENST00000237612.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ABCG2 | ENST00000237612.8 | c.791_792del | p.Leu264HisfsTer14 | frameshift_variant | 7/16 | 1 | NM_004827.3 | P1 | |
ABCG2 | ENST00000515655.5 | c.791_792del | p.Leu264HisfsTer14 | frameshift_variant | 7/16 | 1 | |||
ABCG2 | ENST00000650821.1 | c.791_792del | p.Leu264HisfsTer14 | frameshift_variant | 8/17 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152170Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000279 AC: 7AN: 251134Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135706
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GnomAD4 exome AF: 0.0000431 AC: 63AN: 1461828Hom.: 0 AF XY: 0.0000495 AC XY: 36AN XY: 727218
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GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152170Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74344
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Pathogenic:1Uncertain:2Other:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Al Jalila Children's Genomics Center, Al Jalila Childrens Speciality Hospital | Dec 17, 2022 | - - |
not specified Uncertain:1
Uncertain significance, flagged submission | clinical testing | Al Jalila Children's Genomics Center, Al Jalila Childrens Speciality Hospital | Feb 07, 2021 | - - |
Uric acid concentration, serum, quantitative trait locus 1;C3280986:Blood group, Junior system Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Mar 01, 2022 | - - |
Blood group, Junior system Other:1
Affects, no assertion criteria provided | literature only | OMIM | Jan 15, 2012 | - - |
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