NM_001202.6(BMP4):c.817G>C (p.Val273Leu) AND multiple conditions

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

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 25, 2023
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:: RCV003787021.1

Allele description

NM_001202.6(BMP4):c.817G>C (p.Val273Leu)

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.817G>C (p.Val273Leu)

HGVS:

NC_000014.9:g.53950442C>G
NG_009215.1:g.11395G>C
NM_001202.6:c.817G>CMANE SELECT
NM_001347912.1:c.958G>C
NM_001347913.2:c.628G>C
NM_001347914.2:c.817G>C
NM_001347915.2:c.628G>C
NM_001347916.1:c.817G>C
NM_001347917.1:c.628G>C
NM_130850.5:c.817G>C
NM_130851.4:c.817G>C
NP_001193.2:p.Val273Leu
NP_001334841.1:p.Val320Leu
NP_001334842.1:p.Val210Leu
NP_001334843.1:p.Val273Leu
NP_001334844.1:p.Val210Leu
NP_001334845.1:p.Val273Leu
NP_001334846.1:p.Val210Leu
NP_570911.2:p.Val273Leu
NP_570912.2:p.Val273Leu
NC_000014.8:g.54417160C>G

Protein change:

V210L

Molecular consequence:

NM_001202.6:c.817G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001347912.1:c.958G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001347913.2:c.628G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001347914.2:c.817G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001347915.2:c.628G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001347916.1:c.817G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001347917.1:c.628G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_130850.5:c.817G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_130851.4:c.817G>C - 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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004574216	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 25, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004574216

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 25, 2023)

germline

clinical testing

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

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

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, SCV004574216.1

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

Description

This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 273 of the BMP4 protein (p.Val273Leu). This variant is present in population databases (rs775995114, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with BMP4-related conditions. 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) performed at Invitae indicates that this missense variant is not expected to disrupt BMP4 protein function with a negative predictive value of 80%. 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.

#	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: Mar 5, 2024

ClinVar

Relating variation to medicine