rs1557020021
Variant summary
Our verdict is Pathogenic. The variant received 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_002049.4(GATA1):c.89C>G(p.Ser30*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★).
Frequency
Consequence
NM_002049.4 stop_gained
Scores
Clinical Significance
Conservation
Publications
- GATA1-Related X-Linked CytopeniaInheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
- thrombocytopenia, X-linked, with or without dyserythropoietic anemiaInheritance: XL Classification: STRONG, MODERATE Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
- beta-thalassemia-X-linked thrombocytopenia syndromeInheritance: XL Classification: MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet
- Diamond-Blackfan anemiaInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- cutaneous porphyriaInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
- thrombocytopenia with congenital dyserythropoietic anemiaInheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
- X-linked dyserythropoetic anemia with abnormal platelets and neutropeniaInheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Our verdict: Pathogenic. The variant received 18 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 23
GnomAD4 exome Cov.: 32
GnomAD4 genome Cov.: 23
ClinVar
Submissions by phenotype
Diamond-Blackfan anemia;C1845837:GATA binding protein 1 related thrombocytopenia with dyserythropoiesis Pathogenic:1
For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in GATA1 are known to be pathogenic (PMID: 16783379, 22706301, 23704091, 24453067). This variant has not been reported in the literature in individuals with GATA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 465134). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Ser30*) in the GATA1 gene. It is expected to result in an absent or disrupted protein product. -
Acute megakaryoblastic leukemia in down syndrome Pathogenic:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at