NM_014967.5(FAN1):c.972_973del (p.His324fs) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 31, 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:: RCV003552192.2

Allele description [Variation Report for NM_014967.5(FAN1):c.972_973del (p.His324fs)]

NM_014967.5(FAN1):c.972_973del (p.His324fs)

Gene:

FAN1:FANCD2 and FANCI associated nuclease 1 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

15q13.3

Genomic location:

Preferred name:

NM_014967.5(FAN1):c.972_973del (p.His324fs)

HGVS:

NC_000015.10:g.30905635_30905636del
NG_032946.2:g.6784_6785del
NM_001146094.2:c.972_973del
NM_001146095.1:c.972_973del
NM_001146096.2:c.972_973del
NM_014967.5:c.972_973delMANE SELECT
NP_001139566.1:p.His324fs
NP_001139567.1:p.His324fs
NP_001139568.1:p.His324fs
NP_055782.3:p.His324fs
NC_000015.9:g.31197837_31197838del
NC_000015.9:g.31197838_31197839del

Protein change:

H324fs

Molecular consequence:

NM_001146094.2:c.972_973del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001146095.1:c.972_973del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001146096.2:c.972_973del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_014967.5:c.972_973del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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
SCV004262958	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 31, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 22772369, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004262958

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 31, 2023)

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

FAN1 mutations cause karyomegalic interstitial nephritis, linking chronic kidney failure to defective DNA damage repair.

Zhou W, Otto EA, Cluckey A, Airik R, Hurd TW, Chaki M, Diaz K, Lach FP, Bennett GR, Gee HY, Ghosh AK, Natarajan S, Thongthip S, Veturi U, Allen SJ, Janssen S, Ramaswami G, Dixon J, Burkhalter F, Spoendlin M, Moch H, Mihatsch MJ, et al.

Nat Genet. 2012 Jul 8;44(8):910-5. doi: 10.1038/ng.2347.

PubMed [citation]

PMID:: 22772369
PMCID:: PMC3412140

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV004262958.1

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

Description

This sequence change creates a premature translational stop signal (p.His324Glnfs*5) in the FAN1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in FAN1 are known to be pathogenic (PMID: 22772369). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with FAN1-related conditions. For these reasons, this variant has been classified as Pathogenic.

#	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: Sep 29, 2024

ClinVar

Relating variation to medicine