NM_014334.4(FRRS1L):c.566del (p.Pro189fs) AND Developmental and epileptic encephalopathy, 37

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 22, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV001383854.5

Allele description [Variation Report for NM_014334.4(FRRS1L):c.566del (p.Pro189fs)]

NM_014334.4(FRRS1L):c.566del (p.Pro189fs)

Gene:

FRRS1L:ferric chelate reductase 1 like [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

9q31.3

Genomic location:

Preferred name:

NM_014334.4(FRRS1L):c.566del (p.Pro189fs)

Other names:

p.Pro240Leufs*22

HGVS:

NC_000009.12:g.109141488del
NG_051235.1:g.30806del
NM_014334.3:c.719del
NM_014334.4:c.566delMANE SELECT
NP_055149.3:p.Pro189fs
NC_000009.11:g.111903766del
NC_000009.11:g.111903768del
NM_014334.2:c.719del

Protein change:

P189fs

Links:

dbSNP: rs1831184766

NCBI 1000 Genomes Browser:

rs1831184766

Molecular consequence:

NM_014334.4:c.566del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Developmental and epileptic encephalopathy, 37 (DEE37)
Synonyms:: Epileptic encephalopathy, early infantile, 37
Identifiers:: MONDO: MONDO:0014859; MedGen: C4310770; OMIM: 616981

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001583165	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 22, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 27236917, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001583165

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 22, 2022)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

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

Citations

PubMed

Loss-of-Function Mutations in FRRS1L Lead to an Epileptic-Dyskinetic Encephalopathy.

Madeo M, Stewart M, Sun Y, Sahir N, Wiethoff S, Chandrasekar I, Yarrow A, Rosenfeld JA, Yang Y, Cordeiro D, McCormick EM, Muraresku CC, Jepperson TN, McBeth LJ, Seidahmed MZ, El Khashab HY, Hamad M, Azzedine H, Clark K, Corrochano S, Wells S, Elting MW, et al.

Am J Hum Genet. 2016 Jun 2;98(6):1249-1255. doi: 10.1016/j.ajhg.2016.04.008. Epub 2016 May 26.

PubMed [citation]

PMID:: 27236917
PMCID:: PMC4908178

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV001583165.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1071396). This variant has not been reported in the literature in individuals affected with FRRS1L-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Pro240Leufs*22) in the FRRS1L gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in FRRS1L are known to be pathogenic (PMID: 27236917).

#	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: Oct 8, 2024

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