NM_001202.6(BMP4):c.416G>A (p.Arg139His) AND multiple conditions

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 24, 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:: RCV002982819.2

Allele description

NM_001202.6(BMP4):c.416G>A (p.Arg139His)

Gene:

BMP4:bone morphogenetic protein 4 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

14q22.2

Genomic location:

Preferred name:

NM_001202.6(BMP4):c.416G>A (p.Arg139His)

HGVS:

NC_000014.9:g.53950843C>T
NG_009215.1:g.10994G>A
NM_001202.6:c.416G>AMANE SELECT
NM_001347912.1:c.557G>A
NM_001347913.2:c.227G>A
NM_001347914.2:c.416G>A
NM_001347915.2:c.227G>A
NM_001347916.1:c.416G>A
NM_001347917.1:c.227G>A
NM_130850.5:c.416G>A
NM_130851.4:c.416G>A
NP_001193.2:p.Arg139His
NP_001334841.1:p.Arg186His
NP_001334842.1:p.Arg76His
NP_001334843.1:p.Arg139His
NP_001334844.1:p.Arg76His
NP_001334845.1:p.Arg139His
NP_001334846.1:p.Arg76His
NP_570911.2:p.Arg139His
NP_570912.2:p.Arg139His
NC_000014.8:g.54417561C>T

Protein change:

R139H

Molecular consequence:

NM_001202.6:c.416G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001347912.1:c.557G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001347913.2:c.227G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001347914.2:c.416G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001347915.2:c.227G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001347916.1:c.416G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001347917.1:c.227G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_130850.5:c.416G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_130851.4:c.416G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Microphthalmia with brain and digit anomalies (MCOPS6)
Synonyms:: Microphthalmia syndromic 6; Microphthalmia and pituitary anomalies; Microphthalmia with brain and digit developmental anomalies; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0011936; MedGen: C1864689; Orphanet: 139471; OMIM: 607932

Name:: Orofacial cleft 11 (OFC11)
Synonyms:: CLEFT LIP WITH OR WITHOUT CLEFT PALATE, NONSYNDROMIC, 11; Orofacial cleft 11; ofc11
Identifiers:: MONDO: MONDO:0010906; MedGen: C2677434; OMIM: 600625

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003295311	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 24, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 31063268, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003295311

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 24, 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

Accumulation of rare coding variants in genes implicated in risk of human cleft lip with or without cleft palate.

Marini NJ, Asrani K, Yang W, Rine J, Shaw GM.

Am J Med Genet A. 2019 Jul;179(7):1260-1269. doi: 10.1002/ajmg.a.61183. Epub 2019 May 7.

PubMed [citation]

PMID:: 31063268
PMCID:: PMC6557678

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 Invitae, SCV003295311.2

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

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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C25"). This missense change has been observed in individual(s) with clinical features of BMP4-related conditions (PMID: 31063268). This variant is present in population databases (rs773804981, gnomAD 0.009%). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 139 of the BMP4 protein (p.Arg139His).

#	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: Feb 28, 2024

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