NM_006343.3(MERTK):c.1605-2A>G AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 3, 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:: RCV001071534.6

Allele description [Variation Report for NM_006343.3(MERTK):c.1605-2A>G]

NM_006343.3(MERTK):c.1605-2A>G

Gene:

MERTK:MER proto-oncogene, tyrosine kinase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q13

Genomic location:

Preferred name:

NM_006343.3(MERTK):c.1605-2A>G

HGVS:

NC_000002.12:g.112001199A>G
NG_011607.1:g.107586A>G
NM_006343.3:c.1605-2A>GMANE SELECT
NC_000002.11:g.112758776A>G
NM_006343.2:c.1605-2A>G

Note:

NCBI staff reviewed the sequence information reported in PubMed 11062461 Fig. 1 to determine the location of this allele on the current reference sequence.

Nucleotide change:

IVS10AS, A-G, -2

Links:

OMIM: 604705.0002; dbSNP: rs730880273

NCBI 1000 Genomes Browser:

rs730880273

Molecular consequence:

NM_006343.3:c.1605-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001236842	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 3, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 16199547, 24265693, 29659094, 11062461, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001236842

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 3, 2023)

germline

clinical testing

PubMed (5)
[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

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]

PMID:: 16199547
PMCID:: PMC1735933

Increasing the yield in targeted next-generation sequencing by implicating CNV analysis, non-coding exons and the overall variant load: the example of retinal dystrophies.

Eisenberger T, Neuhaus C, Khan AO, Decker C, Preising MN, Friedburg C, Bieg A, Gliem M, Charbel Issa P, Holz FG, Baig SM, Hellenbroich Y, Galvez A, Platzer K, Wollnik B, Laddach N, Ghaffari SR, Rafati M, Botzenhart E, Tinschert S, Börger D, Bohring A, et al.

PLoS One. 2013;8(11):e78496. doi: 10.1371/journal.pone.0078496. Erratum in: PLoS One. 2014;9(11):e108840.

PubMed [citation]

PMID:: 24265693
PMCID:: PMC3827063

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001236842.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change affects an acceptor splice site in intron 10 of the MERTK gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in MERTK are known to be pathogenic (PMID: 24265693, 29659094). This variant is present in population databases (rs730880273, gnomAD 0.01%). Disruption of this splice site has been observed in individuals with retinitis pigmentosa (PMID: 11062461; Invitae). This variant is also known as IVS10-2A>G. ClinVar contains an entry for this variant (Variation ID: 5401). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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

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