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NM_001101.5(ACTB):c.589G>A (p.Gly197Ser) AND Baraitser-Winter syndrome 1

Germline classification:
Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:
May 8, 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:
RCV001305813.8

Allele description [Variation Report for NM_001101.5(ACTB):c.589G>A (p.Gly197Ser)]

NM_001101.5(ACTB):c.589G>A (p.Gly197Ser)

Gene:
ACTB:actin beta [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
7p22.1
Genomic location:
Preferred name:
NM_001101.5(ACTB):c.589G>A (p.Gly197Ser)
HGVS:
  • NC_000007.14:g.5528494C>T
  • NG_007992.1:g.7108G>A
  • NM_001101.5:c.589G>AMANE SELECT
  • NP_001092.1:p.Gly197Ser
  • LRG_132t1:c.589G>A
  • LRG_132:g.7108G>A
  • NC_000007.13:g.5568125C>T
  • NM_001101.3:c.589G>A
Protein change:
G197S
Links:
dbSNP: rs1554329317
NCBI 1000 Genomes Browser:
rs1554329317
Molecular consequence:
  • NM_001101.5:c.589G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Baraitser-Winter syndrome 1 (BRWS1)
Synonyms:
Iris coloboma with ptosis, hypertelorism, and mental retardation; BARAITSER-WINTER SYNDROME 1, ATYPICAL; PACHYGYRIA, MENTAL RETARDATION, EPILEPSY, AND CHARACTERISTIC FACIES; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0009470; MedGen: C1855722; Orphanet: 2649; Orphanet: 2995; OMIM: 243310

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001495161Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Likely pathogenic
(May 8, 2023)
germlineclinical testing

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

SCV002760063Laboratory of Medical Genetics, University of Torino - NeuroWES
criteria provided, single submitter

(ACMG Guidelines, 2015)
Pathogenic
(Nov 29, 2022)
germlineresearch

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providedgermlineyesnot providednot providednot providednot providednot providedresearch

Citations

PubMed

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

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 Invitae, SCV001495161.4

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

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on ACTB protein function. ClinVar contains an entry for this variant (Variation ID: 522017). This missense change has been observed in individual(s) with clinical features of ACTB-related conditions and/or clinical features of Baraitser-Winter syndrome (Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 197 of the ACTB protein (p.Gly197Ser).

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

From Laboratory of Medical Genetics, University of Torino - NeuroWES, SCV002760063.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedresearch PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jun 23, 2024