NM_021871.4(FGA):c.104G>A (p.Arg35His) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Apr 9, 2024
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:: RCV001509236.12

Allele description [Variation Report for NM_021871.4(FGA):c.104G>A (p.Arg35His)]

NM_021871.4(FGA):c.104G>A (p.Arg35His)

Gene:

FGA:fibrinogen alpha chain [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

4q31.3

Genomic location:

Preferred name:

NM_021871.4(FGA):c.104G>A (p.Arg35His)

Other names:

R16H; FIBRINOGEN AMIENS 1; FIBRINOGEN AMIENS 2; FIBRINOGEN BERGAMO 3; FIBRINOGEN BERN 2; FIBRINOGEN BICETRE 1; FIBRINOGEN BIRMINGHAM 1; FIBRINOGEN CHAPEL HILL 2; FIBRINOGEN CLERMONT-FERRAND 1; FIBRINOGEN GIESSEN 1; FIBRINOGEN LEITCHFIELD; FIBRINOGEN LONG BEACH 1; FIBRINOGEN LOUISVILLE 1; FIBRINOGEN MANCHESTER 1; FIBRINOGEN PARIS 6; FIBRINOGEN PETOSKEY 1; FIBRINOGEN SEATTLE 2; FIBRINOGEN SHEFFIELD 2; FIBRINOGEN SYDNEY 1; FIBRINOGEN SYDNEY 2; FIBRINOGEN WHITE MARSH 1; Fibrinogen Petoskey

HGVS:

NC_000004.12:g.154589513C>T
NG_008832.1:g.6233G>A
NM_000508.5:c.104G>A
NM_021871.4:c.104G>AMANE SELECT
NP_000499.1:p.Arg35His
NP_068657.1:p.Arg35His
LRG_557t1:c.104G>A
LRG_557t2:c.104G>A
LRG_557:g.6233G>A
LRG_557p1:p.Arg35His
NC_000004.11:g.155510665C>T
NM_000508.3:c.104G>A
NM_000508.4:c.104G>A
NM_021871.2:c.104G>A
NM_021871.3:c.104G>A
NM_021871.4:c.104G>A
P02671:p.Arg35His

Protein change:

R35H; ARG16HIS

Links:

UniProtKB: P02671#VAR_002393; OMIM: 134820.0004; dbSNP: rs121909607

NCBI 1000 Genomes Browser:

rs121909607

Molecular consequence:

NM_000508.5:c.104G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_021871.4:c.104G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001715840	Mayo Clinic Laboratories, Mayo Clinic	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jan 4, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001874102	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Apr 9, 2024)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001715840

Mayo Clinic Laboratories, Mayo Clinic

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jan 4, 2023)

germline

clinical testing

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

SCV001874102

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Apr 9, 2024)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	17	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 Mayo Clinic Laboratories, Mayo Clinic, SCV001715840.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	17	not provided	not provided	clinical testing	PubMed (1)

Description

PM1, PM2, PM5, PS3, PS4_moderate

#	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		17	not provided	not provided	not provided

From GeneDx, SCV001874102.6

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

Description

Published functional studies suggest a damaging effect: impaired thrombin polymerization, reduced fibrinogen clottability, reduced fibrinolysis velocity, and delayed release of fibrinopeptide A (PMID: 6830702, 22967385, 22880226); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at a significant frequency in large population cohorts (gnomAD); Also known as R16H using alternate nomenclature; This variant is associated with the following publications: (PMID: 32877852, 33822462, 33443927, 34275736, 32939696, 23962069, 22880226, 22967385, 6830702, 27684817, 6191801, 2738154, 9391726, 25320241, 26577257, 29070135, 29869737, 30856382, 31314131, 30332696, 32166693, 30349899, 2379562, 35949040, 35975558, 31064749, 3618591, 34455742, 7298640, 22169505)

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

Last Updated: Nov 24, 2024

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