NM_000492.4(CFTR):c.929TCT[2] (p.Phe312del) AND not provided

Germline classification:: Pathogenic/Likely pathogenic (5 submissions)
Last evaluated:: Nov 15, 2022
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:: RCV000759769.26

Allele description [Variation Report for NM_000492.4(CFTR):c.929TCT[2] (p.Phe312del)]

NM_000492.4(CFTR):c.929TCT[2] (p.Phe312del)

Gene:

CFTR:CF transmembrane conductance regulator [Gene - OMIM - HGNC]

Variant type:

Microsatellite

Cytogenetic location:

7q31.2

Genomic location:

Preferred name:

NM_000492.4(CFTR):c.929TCT[2] (p.Phe312del)

Other names:

[delta]F311

HGVS:

NC_000007.13:g.117180219_117180221delTCT
NC_000007.14:g.117540159TCT[2]
NG_016465.4:g.79376TCT[2]
NM_000492.4:c.929TCT[2]MANE SELECT
NP_000483.3:p.Phe312del
LRG_663t1:c.935_937del
LRG_663:g.79376TCT[2]
NC_000007.13:g.117180211_117180213del
NC_000007.13:g.117180213TCT[2]
NC_000007.13:g.117180219_117180221del
NC_000007.13:g.117180219_117180221delTCT
NC_000007.14:g.117540165_117540167del
NM_000492.3:c.933_935delCTT
NM_000492.3:c.935_937delTCT
NM_000492.4:c.935_937delMANE SELECT

Protein change:

F312del

Links:

dbSNP: rs121908768

NCBI 1000 Genomes Browser:

rs121908768

Molecular consequence:

NM_000492.4:c.929TCT[2] - inframe_deletion - [Sequence Ontology: SO:0001822]

Observations:

Condition(s)

Synonyms:: none provided; RECLASSIFIED - ADRA2C POLYMORPHISM; RECLASSIFIED - ADRB1 POLYMORPHISM
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000331527	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions)	Pathogenic (Nov 19, 2013)	germline	clinical testing	Citation Link,
SCV000889318	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Pathogenic (Oct 12, 2017)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001160472	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process)	Likely pathogenic (Jun 19, 2020)	germline	clinical testing	Citation Link,
SCV002525766	Mayo Clinic Laboratories, Mayo Clinic	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Nov 15, 2022)	germline	clinical testing	PubMed (8) [See all records that cite these PMIDs] 18456578, 22975760, 31036917, 34134972, 34782259, 35315358, 7509232, 25741868
SCV003826302	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Aug 23, 2022)	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	5	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.

Karbassi I, Maston GA, Love A, DiVincenzo C, Braastad CD, Elzinga CD, Bright AR, Previte D, Zhang K, Rowland CM, McCarthy M, Lapierre JL, Dubois F, Medeiros KA, Batish SD, Jones J, Liaquat K, Hoffman CA, Jaremko M, Wang Z, Sun W, Buller-Burckle A, et al.

Hum Mutat. 2016 Jan;37(1):127-34. doi: 10.1002/humu.22918. Epub 2015 Oct 29.

PubMed [citation]

PMID:: 26467025
PMCID:: PMC4737317

Consensus on the use and interpretation of cystic fibrosis mutation analysis in clinical practice.

Castellani C, Cuppens H, Macek M Jr, Cassiman JJ, Kerem E, Durie P, Tullis E, Assael BM, Bombieri C, Brown A, Casals T, Claustres M, Cutting GR, Dequeker E, Dodge J, Doull I, Farrell P, Ferec C, Girodon E, Johannesson M, Kerem B, Knowles M, et al.

J Cyst Fibros. 2008 May;7(3):179-96. doi: 10.1016/j.jcf.2008.03.009. Review.

PubMed [citation]

PMID:: 18456578
PMCID:: PMC2810954

See all PubMed Citations (9)

Details of each submission

From Eurofins Ntd Llc (ga), SCV000331527.4

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

#	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		2	not provided	not provided	not provided

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV000889318.2

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

#	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

From ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV001160472.2

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

Description

The CFTR c.935_937delTCT; p.Phe312del variant (rs121908768), also known as F311del, is reported in the literature in multiple individuals affected with cystic fibrosis and has been found in affected individuals in trans to the pathogenic p.Phe508del variant (Friedman 1998, Meitinger 1993). The p.Phe312del variant is also frequently observed in African-American and Hispanic cystic fibrosis patients (Kharrazi 2015, Schrijver 2005, Sugarman 2004, Watts 2012). This variant is reported as pathogenic by multiple laboratories in ClinVar (Variation ID: 48704) and is found in the general population with an overall allele frequency of 0.008% (19/251076 alleles, including one homozygote) in the Genome Aggregation Database. This variant deletes a highly conserved phenylalanine residue, leaving the rest of the protein in-frame. Based on available information, the p.Phe312del variant is considered to be likely pathogenic. REFERENCES Friedman K et al. Cystic fibrosis transmembrane-conductance regulator mutations among African Americans. Am J Hum Genet. 1998 62(1):195-6. Kharrazi M et al. Newborn Screening for Cystic Fibrosis in California. Pediatrics. 2015 Dec;136(6):1062-72. Meitinger T et al. In frame deletion (delta F311) within a short trinucleotide repeat of the first transmembrane region of the cystic fibrosis gene. Hum Mol Genet. 1993 2(12):2173-4. Schrijver I et al. Diagnostic testing by CFTR gene mutation analysis in a large group of Hispanics: novel mutations and assessment of a population-specific mutation spectrum. J Mol Diagn. 2005 May;7(2):289-99. Sugarman EA et al. CFTR mutation distribution among U.S. Hispanic and African American individuals: evaluation in cystic fibrosis patient and carrier screening populations. Genet Med. 2004 Sep-Oct;6(5):392-9. Watts KD et al. Hispanic Infants with cystic fibrosis show low CFTR mutation detection rates in the Illinois newborn screening program. J Genet Couns. 2012 Oct;21(5):671-5.

#	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

From Mayo Clinic Laboratories, Mayo Clinic, SCV002525766.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	3	not provided	not provided	clinical testing	PubMed (8)

Description

PP5, PM3, PM4

#	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		3	not provided	not provided	not provided

From Revvity Omics, Revvity, SCV003826302.2

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

#	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: Dec 7, 2024

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