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NM_000243.3(MEFV):c.1894G>A (p.Gly632Ser) AND multiple conditions

Germline classification:
Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:
Nov 18, 2020
Review status:
criteria provided, conflicting classifications
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:
RCV000763382.12

Allele description [Variation Report for NM_000243.3(MEFV):c.1894G>A (p.Gly632Ser)]

NM_000243.3(MEFV):c.1894G>A (p.Gly632Ser)

Genes:
LOC126862264:CDK7 strongly-dependent group 2 enhancer GRCh37_chr16:3293322-3294521 [Gene]
MEFV:MEFV innate immunity regulator, pyrin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
16p13.3
Genomic location:
Preferred name:
NM_000243.3(MEFV):c.1894G>A (p.Gly632Ser)
HGVS:
  • NC_000016.10:g.3243593C>T
  • NG_007871.1:g.18035G>A
  • NM_000243.3:c.1894G>AMANE SELECT
  • NM_001198536.2:c.*98G>A
  • NP_000234.1:p.Gly632Ser
  • NP_000234.1:p.Gly632Ser
  • LRG_190t1:c.1894G>A
  • LRG_190:g.18035G>A
  • LRG_190p1:p.Gly632Ser
  • NC_000016.9:g.3293593C>T
  • NM_000243.1:c.1894G>A
  • NM_000243.2:c.1894G>A
  • O15553:p.Gly632Ser
Protein change:
G632S
Links:
UniProtKB: O15553#VAR_028335; dbSNP: rs104895128
NCBI 1000 Genomes Browser:
rs104895128
Molecular consequence:
  • NM_001198536.2:c.*98G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_000243.3:c.1894G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Familial Mediterranean fever (FMF)
Synonyms:
POLYSEROSITIS, FAMILIAL PAROXYSMAL; POLYSEROSITIS, RECURRENT; Periodic peritonitis; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0018088; MedGen: C0031069; Orphanet: 342; OMIM: 249100
Name:
Familial Mediterranean fever, autosomal dominant
Synonyms:
FMF, AUTOSOMAL DOMINANT; Dominant Familial Mediterranean Fever
Identifiers:
MONDO: MONDO:0007601; MedGen: C1851347; Orphanet: 342; OMIM: 134610

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000894081Fulgent Genetics, Fulgent Genetics
criteria provided, single submitter

(ACMG Guidelines, 2015)		Likely pathogenic
(Oct 31, 2018) 		unknownclinical testing

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

SCV002495840Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Nov 18, 2020) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providedunknownunknownnot providednot providednot providednot providednot providedclinical 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
PMC

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.

Genetics in medicine : official journal of the American College of Medical Genetics. 2015 Mar 5; 17(5): 405-424

PMC [article]
PMCID:
PMC4544753
PMID:
25741868
DOI:
10.1038/gim.2015.30

Details of each submission

From Fulgent Genetics, Fulgent Genetics, SCV000894081.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago, SCV002495840.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

MEFV NM_000243.2 exon 10 p.Gly632Ser (c.1894G>A): This variant has been reported in the literature in the heterozygous and compound heterozygous state in at least 3 individuals with Familial Mediterranean Fever (FMF), potentially segregating with disease in at least 2 affected family members (Shinar 2007 PMID:17938136). This variant has also been reported in at least 1 individual with adult onset Still's disease (Nonaka 2015 PMID:25286988, Umeda 2017 PMID:27310525). This variant is present in 0.001% (1/68022) of European alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/16-3243593-C-T?dataset=gnomad_r3). This variant is present in ClinVar (Variation ID:97467). This variant amino acid Serine (Ser) is present in >20 species including mammals and is not well conserved among evolutionarily distant species; this suggests that this variant may not impact the protein. Additional computational prediction tools do not suggest an impact. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 3, 2024