NM_000038.6(APC):c.4778del (p.Lys1593fs) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: May 7, 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:: RCV000657448.2

Allele description [Variation Report for NM_000038.6(APC):c.4778del (p.Lys1593fs)]

NM_000038.6(APC):c.4778del (p.Lys1593fs)

Gene:

APC:APC regulator of WNT signaling pathway [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

5q22.2

Genomic location:

Preferred name:

NM_000038.6(APC):c.4778del (p.Lys1593fs)

Other names:

NM_000038.6(APC):c.4778del; p.Lys1593fs

HGVS:

NC_000005.10:g.112840372del
NG_008481.4:g.152852del
NM_000038.5:c.4778del
NM_000038.6:c.4778delMANE SELECT
NM_001127510.3:c.4778del
NM_001127511.3:c.4724del
NM_001354895.2:c.4778del
NM_001354896.2:c.4832del
NM_001354897.2:c.4808del
NM_001354898.2:c.4703del
NM_001354899.2:c.4694del
NM_001354900.2:c.4655del
NM_001354901.2:c.4601del
NM_001354902.2:c.4505del
NM_001354903.2:c.4475del
NM_001354904.2:c.4400del
NM_001354905.2:c.4298del
NM_001354906.2:c.3929del
NP_000029.2:p.Lys1593fs
NP_001120982.1:p.Lys1593fs
NP_001120983.2:p.Lys1575fs
NP_001341824.1:p.Lys1593fs
NP_001341825.1:p.Lys1611fs
NP_001341826.1:p.Lys1603fs
NP_001341827.1:p.Lys1568fs
NP_001341828.1:p.Lys1565fs
NP_001341829.1:p.Lys1552fs
NP_001341830.1:p.Lys1534fs
NP_001341831.1:p.Lys1502fs
NP_001341832.1:p.Lys1492fs
NP_001341833.1:p.Lys1467fs
NP_001341834.1:p.Lys1433fs
NP_001341835.1:p.Lys1310fs
LRG_130:g.152852del
NC_000005.9:g.112176069del
NM_000038.5:c.4778delA

Protein change:

K1310fs

Links:

dbSNP: rs1554086185

NCBI 1000 Genomes Browser:

rs1554086185

Molecular consequence:

NM_000038.6:c.4778del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001127510.3:c.4778del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001127511.3:c.4724del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354895.2:c.4778del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354896.2:c.4832del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354897.2:c.4808del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354898.2:c.4703del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354899.2:c.4694del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354900.2:c.4655del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354901.2:c.4601del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354902.2:c.4505del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354903.2:c.4475del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354904.2:c.4400del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354905.2:c.4298del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354906.2:c.3929del - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV000779183	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Pathogenic (Jan 11, 2018)	germline	clinical testing	Citation Link,
SCV004219466	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Pathogenic (May 7, 2023)	unknown	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

SCV000779183

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Pathogenic
(Jan 11, 2018)

germline

clinical testing

Citation Link,

SCV004219466

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Pathogenic
(May 7, 2023)

unknown

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	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	not provided	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

Details of each submission

From GeneDx, SCV000779183.1

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

Description

This deletion of one nucleotide in APC is denoted c.4778delA at the cDNA level and p.Lys1593SerfsX57 (K1593SfsX57) at the protein level. The normal sequence, with the base that is deleted in brackets, is CAAAAA[delA]GCCA. The deletion causes a frameshift which changes a Lysine to a Serine at codon 1593, and creates a premature stop codon at position 57 of the new reading frame. Although this variant has not, to our knowledge, been reported in the literature, it is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. We consider this variant to be pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV004219466.1

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

Description

This frameshift variant alters the translational reading frame of the APC mRNA and causes the premature termination of APC protein synthesis. This variant has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). To the best of our knowledge, the variant has not been reported in the published literature. Based on the available information, this variant is classified as pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: May 16, 2025

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