NM_015474.4(SAMHD1):c.696+2T>C AND Aicardi-Goutieres syndrome 5

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jan 1, 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:: RCV003610377.2

Allele description [Variation Report for NM_015474.4(SAMHD1):c.696+2T>C]

NM_015474.4(SAMHD1):c.696+2T>C

Gene:

SAMHD1:SAM and HD domain containing deoxynucleoside triphosphate triphosphohydrolase 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

20q11.23

Genomic location:

Preferred name:

NM_015474.4(SAMHD1):c.696+2T>C

HGVS:

NC_000020.11:g.36927180A>G
NG_017059.1:g.29664T>C
NM_001363729.2:c.696+2T>C
NM_001363733.2:c.696+2T>C
NM_015474.4:c.696+2T>CMANE SELECT
LRG_281:g.29664T>C
NC_000020.10:g.35555583A>G

Molecular consequence:

NM_001363729.2:c.696+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001363733.2:c.696+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_015474.4:c.696+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:: Aicardi-Goutieres syndrome 5
Identifiers:: MONDO: MONDO:0013059; MedGen: C2749659; Orphanet: 51; OMIM: 612952

Recent activity

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Dolycoris indicus voucher YNYY mitochondrion, complete genome
Dolycoris indicus voucher YNYY mitochondrion, complete genome
gi|2687671898|gb|OQ909517.1|

Nucleotide
Triatoma brasiliensis brasiliensis haplotype 21 cytochrome b gene, partial cds; ...
Triatoma brasiliensis brasiliensis haplotype 21 cytochrome b gene, partial cds; mitochondrial
gi|2675109316|gb|PP316005.1|

Nucleotide
ctnnbl1 catenin, beta like 1 [Danio rerio]
ctnnbl1 catenin, beta like 1 [Danio rerio]
Gene ID:393840

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004426172	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Jan 1, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 16199547, 19525956, 22461318, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004426172

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Jan 1, 2023)

germline

clinical testing

PubMed (4)
[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

Mutations involved in Aicardi-Goutières syndrome implicate SAMHD1 as regulator of the innate immune response.

Rice GI, Bond J, Asipu A, Brunette RL, Manfield IW, Carr IM, Fuller JC, Jackson RM, Lamb T, Briggs TA, Ali M, Gornall H, Couthard LR, Aeby A, Attard-Montalto SP, Bertini E, Bodemer C, Brockmann K, Brueton LA, Corry PC, Desguerre I, Fazzi E, et al.

Nat Genet. 2009 Jul;41(7):829-32. doi: 10.1038/ng.373. Epub 2009 Jun 14.

PubMed [citation]

PMID:: 19525956
PMCID:: PMC4154505

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004426172.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This variant has not been reported in the literature in individuals affected with SAMHD1-related conditions. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 6 of the SAMHD1 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 SAMHD1 are known to be pathogenic (PMID: 19525956, 22461318).

#	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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