NM_001077415.3(CRELD1):c.658C>T (p.Arg220Ter) AND Atrioventricular septal defect, susceptibility to, 2

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Dec 28, 2020
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:: RCV001196762.6

Allele description [Variation Report for NM_001077415.3(CRELD1):c.658C>T (p.Arg220Ter)]

NM_001077415.3(CRELD1):c.658C>T (p.Arg220Ter)

Gene:

CRELD1:cysteine rich with EGF like domains 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3p25.3

Genomic location:

Preferred name:

NM_001077415.3(CRELD1):c.658C>T (p.Arg220Ter)

HGVS:

NC_000003.12:g.9941131C>T
NG_017069.1:g.12291C>T
NM_001031717.4:c.658C>T
NM_001077415.3:c.658C>TMANE SELECT
NM_001374316.1:c.658C>T
NM_001374317.1:c.658C>T
NM_001374318.1:c.658C>T
NM_001374319.1:c.658C>T
NM_001374320.1:c.658C>T
NM_015513.6:c.658C>T
NP_001026887.2:p.Arg220Ter
NP_001070883.2:p.Arg220Ter
NP_001361245.1:p.Arg220Ter
NP_001361246.1:p.Arg220Ter
NP_001361247.1:p.Arg220Ter
NP_001361248.1:p.Arg220Ter
NP_001361249.1:p.Arg220Ter
NP_056328.3:p.Arg220Ter
NC_000003.11:g.9982815C>T
NC_000003.11:g.9982815C>T
NM_001031717.3:c.658C>T
NR_164475.1:n.686C>T
NR_164476.1:n.662C>T
NR_164477.1:n.1036C>T

Protein change:

R220*

Links:

dbSNP: rs1433259474

NCBI 1000 Genomes Browser:

rs1433259474

Molecular consequence:

NR_164475.1:n.686C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_164476.1:n.662C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_164477.1:n.1036C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_001031717.4:c.658C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001077415.3:c.658C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001374316.1:c.658C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001374317.1:c.658C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001374318.1:c.658C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001374319.1:c.658C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001374320.1:c.658C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_015513.6:c.658C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Atrioventricular septal defect, susceptibility to, 2
Synonyms:: Atrioventricular septal defect 2
Identifiers:: MONDO: MONDO:0011650; MedGen: C1853508; OMIM: 606217

Recent activity

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Danio rerio zgc:92006, mRNA (cDNA clone MGC:92006 IMAGE:7043610), complete cds
Danio rerio zgc:92006, mRNA (cDNA clone MGC:92006 IMAGE:7043610), complete cds
gi|50418113|gb|BC078405.1|

Nucleotide
hnRNP-E2 protein [Xenopus laevis]
hnRNP-E2 protein [Xenopus laevis]
gi|5459450|emb|CAB50743.1|

Protein
LOC100007137 [Danio rerio]
LOC100007137 [Danio rerio]
Gene ID:100007137

Gene
tmem176l.4 [Danio rerio]
tmem176l.4 [Danio rerio]
Gene ID:571746

Gene
ft2 alpha(1,3)fucosyltransferase gene 2 [Danio rerio]
ft2 alpha(1,3)fucosyltransferase gene 2 [Danio rerio]
Gene ID:30684

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001367395	Centre for Mendelian Genomics, University Medical Centre Ljubljana	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Nov 22, 2019)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002272862	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 28, 2020)	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

SCV001367395

Centre for Mendelian Genomics, University Medical Centre Ljubljana

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Nov 22, 2019)

unknown

clinical testing

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

SCV002272862

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 28, 2020)

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	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	yes	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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Centre for Mendelian Genomics, University Medical Centre Ljubljana, SCV001367395.2

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

Description

This variant was classified as: Uncertain significance. The available evidence on this variant's pathogenicity is insufficient or conflicting. The following ACMG criteria were applied in classifying this variant: PM2,PP3.

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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002272862.3

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

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant has not been reported in the literature in individuals with CRELD1-related conditions. ClinVar contains an entry for this variant (Variation ID: 930822). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Arg220*) in the CRELD1 gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in CRELD1 cause disease.

#	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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