NM_000037.4(ANK1):c.2803C>T (p.Arg935Ter) AND Hereditary spherocytosis type 1

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Apr 25, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001802420.13

Allele description [Variation Report for NM_000037.4(ANK1):c.2803C>T (p.Arg935Ter)]

NM_000037.4(ANK1):c.2803C>T (p.Arg935Ter)

Gene:

ANK1:ankyrin 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

8p11.21

Genomic location:

Preferred name:

NM_000037.4(ANK1):c.2803C>T (p.Arg935Ter)

Other names:

p.Arg935*

HGVS:

NC_000008.11:g.41696520G>A
NG_012820.2:g.205243C>T
NM_000037.4:c.2803C>TMANE SELECT
NM_001142446.2:c.2926C>T
NM_020475.3:c.2803C>T
NM_020476.3:c.2803C>T
NM_020477.3:c.2803C>T
NP_000028.3:p.Arg935Ter
NP_001135918.1:p.Arg976Ter
NP_065208.2:p.Arg935Ter
NP_065209.2:p.Arg935Ter
NP_065210.2:p.Arg935Ter
NC_000008.10:g.41554038G>A
NM_000037.3:c.2803C>T
NM_000037.4:c.2803C>T

Protein change:

R935*

Links:

dbSNP: rs2150597061

NCBI 1000 Genomes Browser:

rs2150597061

Molecular consequence:

NM_000037.4:c.2803C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001142446.2:c.2926C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_020475.3:c.2803C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_020476.3:c.2803C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_020477.3:c.2803C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Hereditary spherocytosis type 1
Synonyms:: Spherocytosis type 1; ANK1-Related Spherocytosis
Identifiers:: MONDO: MONDO:0008447; MedGen: C2674218; Orphanet: 822; OMIM: 182900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002048031	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process 2024)	Pathogenic (Mar 29, 2023)	germline	clinical testing	Citation Link,
SCV002499992	Jiangsu Institute of Hematology, the First Affiliated Hospital of Soochow University	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 1, 2022)	de novo	research	PubMed (1) [See all records that cite this PMID]
SCV003817329	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Apr 25, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002048031

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

criteria provided, single submitter

(ARUP Molecular Germline Variant Investigation Process 2024)

Pathogenic
(Mar 29, 2023)

germline

clinical testing

Citation Link,

SCV002499992

Jiangsu Institute of Hematology, the First Affiliated Hospital of Soochow University

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Mar 1, 2022)

de novo

research

PubMed (1)
[See all records that cite this PMID]

SCV003817329

Revvity Omics, Revvity

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Apr 25, 2023)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	de novo	yes	not provided	not provided	not provided	not provided	not provided	research
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV002048031.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

The ANK1 c.2803C>T; p.Arg935Ter variant is reported in the literature in multiple individuals with spherocytosis or hemolytic anemia (Choi 2019, Del Orbe Barreto 2016, Gao 2018, Muramatsu 2017, Tole 2020, Wang 2018). This variant is also reported in ClinVar (Variation ID: 1330761). This variant is absent from the Genome Aggregation Database, indicating it is not a common polymorphism. This variant induces an early termination codon and is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Based on available information, this variant is considered to be pathogenic. REFERENCES Choi HS et al. Molecular diagnosis of hereditary spherocytosis by multi-gene target sequencing in Korea: matching with osmotic fragility test and presence of spherocyte. Orphanet J Rare Dis. 2019 May 23. PMID: 31122244 Del Orbe Barreto R et al. Detection of new pathogenic mutations in patients with congenital haemolytic anaemia using next-generation sequencing. Int J Lab Hematol. 2016 Dec. PMID: 27427187 Gao Y et al. Diagnosis of Hereditary Spherocytosis and Secondary Hemochromatosis in a Patient with Jaundice. Acta Haematol. 2018 PMID: 29597199 Muramatsu H et al. Clinical utility of next-generation sequencing for inherited bone marrow failure syndromes. Genet Med. 2017 Jul. PMID: 28102861 Tole S et al. Genotype-phenotype correlation in children with hereditary spherocytosis. Br J Haematol. 2020 Nov. PMID: 32436265 Wang R et al. Exome sequencing confirms molecular diagnoses in 38 Chinese families with hereditary spherocytosis. Sci China Life Sci. 2018 Aug. PMID: 29572776

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Jiangsu Institute of Hematology, the First Affiliated Hospital of Soochow University, SCV002499992.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	research	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	de novo	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Revvity Omics, Revvity, SCV003817329.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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