NM_001377299.1(NDUFS2):c.1212G>A (p.Lys404=) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Aug 10, 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:: RCV000199124.6

Allele description [Variation Report for NM_001377299.1(NDUFS2):c.1212G>A (p.Lys404=)]

NM_001377299.1(NDUFS2):c.1212G>A (p.Lys404=)

Gene:

NDUFS2:NADH:ubiquinone oxidoreductase core subunit S2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q23.3

Genomic location:

Preferred name:

NM_001377299.1(NDUFS2):c.1212G>A (p.Lys404=)

Other names:

p.K404K:AAG>AAA

HGVS:

NC_000001.11:g.161213475G>A
NG_013352.1:g.19161G>A
NG_029043.1:g.3179G>A
NM_001166159.2:c.1212G>A
NM_001377298.1:c.1212G>A
NM_001377299.1:c.1212G>AMANE SELECT
NM_001377300.1:c.1212G>A
NM_001377301.1:c.1212G>A
NM_001377302.1:c.1212G>A
NM_004550.5:c.1212G>A
NP_001159631.1:p.Lys404=
NP_001364227.1:p.Lys404=
NP_001364228.1:p.Lys404=
NP_001364229.1:p.Lys404=
NP_001364230.1:p.Lys404=
NP_001364231.1:p.Lys404=
NP_004541.1:p.Lys404=
NP_004541.1:p.Lys404=
NC_000001.10:g.161183265G>A
NM_004550.4:c.1212G>A
NR_165188.1:n.1101G>A

Links:

dbSNP: rs145959971

NCBI 1000 Genomes Browser:

rs145959971

Molecular consequence:

NR_165188.1:n.1101G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_001166159.2:c.1212G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001377298.1:c.1212G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001377299.1:c.1212G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001377300.1:c.1212G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001377301.1:c.1212G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001377302.1:c.1212G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_004550.5:c.1212G>A - synonymous variant - [Sequence Ontology: SO:0001819]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: CN517202

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000251878	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Sep 28, 2021)	germline	clinical testing	Citation Link,
SCV002154265	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 10, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 17576681, 9536098, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000251878

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(Sep 28, 2021)

germline

clinical testing

Citation Link,

SCV002154265

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 10, 2022)

germline

clinical testing

PubMed (3)
[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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization.

Buratti E, Chivers M, Královicová J, Romano M, Baralle M, Krainer AR, Vorechovsky I.

Nucleic Acids Res. 2007;35(13):4250-63. Epub 2007 Jun 18.

PubMed [citation]

PMID:: 17576681
PMCID:: PMC1934990

Statistical features of human exons and their flanking regions.

Zhang MQ.

Hum Mol Genet. 1998 May;7(5):919-32.

PubMed [citation]

PMID:: 9536098

See all PubMed Citations (3)

Details of each submission

From GeneDx, SCV000251878.15

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

Description

In-silico analysis, which includes splice predictors and evolutionary conservation, is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; Has not been previously published as pathogenic or benign to our knowledge

#	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 Invitae, SCV002154265.2

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

Description

This sequence change affects codon 404 of the NDUFS2 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the NDUFS2 protein. This variant also falls at the last nucleotide of exon 12, which is part of the consensus splice site for this exon. This variant is present in population databases (rs145959971, gnomAD 0.07%). This variant has not been reported in the literature in individuals affected with NDUFS2-related conditions. ClinVar contains an entry for this variant (Variation ID: 214796). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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: Oct 28, 2023

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