NM_024753.5(TTC21B):c.1697A>G (p.His566Arg) AND Nephronophthisis 12

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Oct 15, 2018
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:: RCV000755750.6

Allele description [Variation Report for NM_024753.5(TTC21B):c.1697A>G (p.His566Arg)]

NM_024753.5(TTC21B):c.1697A>G (p.His566Arg)

Gene:

TTC21B:tetratricopeptide repeat domain 21B [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q24.3

Genomic location:

Preferred name:

NM_024753.5(TTC21B):c.1697A>G (p.His566Arg)

HGVS:

NC_000002.12:g.165917459T>C
NG_030345.1:g.41380A>G
NM_024753.5:c.1697A>GMANE SELECT
NP_079029.3:p.His566Arg
NC_000002.11:g.166773969T>C
NM_024753.4:c.1697A>G
Q7Z4L5:p.His566Arg

Protein change:

H566R

Links:

UniProtKB: Q7Z4L5#VAR_065529; dbSNP: rs146320075

NCBI 1000 Genomes Browser:

rs146320075

Molecular consequence:

NM_024753.5:c.1697A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Nephronophthisis 12 (NPHP12)
Identifiers:: MONDO: MONDO:0013442; MedGen: C3151186; Orphanet: 655; OMIM: 613820

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000883283	SIB Swiss Institute of Bioinformatics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Oct 15, 2018)	unknown	curation	PubMed (2) [See all records that cite these PMIDs] 21258341, 25741868
SCV001294077	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Uncertain significance (Aug 21, 2017)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000883283

SIB Swiss Institute of Bioinformatics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Oct 15, 2018)

unknown

curation

PubMed (2)
[See all records that cite these PMIDs]

SCV001294077

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 13 December 2019)

Uncertain significance
(Aug 21, 2017)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Citation Link

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
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	curation

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

TTC21B contributes both causal and modifying alleles across the ciliopathy spectrum.

Davis EE, Zhang Q, Liu Q, Diplas BH, Davey LM, Hartley J, Stoetzel C, Szymanska K, Ramaswami G, Logan CV, Muzny DM, Young AC, Wheeler DA, Cruz P, Morgan M, Lewis LR, Cherukuri P, Maskeri B, Hansen NF, Mullikin JC, Blakesley RW, Bouffard GG; et al.

Nat Genet. 2011 Mar;43(3):189-96. doi: 10.1038/ng.756. Epub 2011 Jan 23.

PubMed [citation]

PMID:: 21258341
PMCID:: PMC3071301

Details of each submission

From SIB Swiss Institute of Bioinformatics, SCV000883283.1

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

Description

This variant is interpreted as Uncertain Significance - Conflicting Evidence, for Nephronophthisis 12, autosomal recessive. The following ACMG Tag(s) were applied: PP3 => Multiple lines of computational evidence support a deleterious effect on the gene or gene product. BS1-Supporting => BS1 downgraded in strength to supporting. PS3 => Well-established functional studies show a deleterious effect (https://www.ncbi.nlm.nih.gov/pubmed/21258341).

#	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

From Illumina Laboratory Services, Illumina, SCV001294077.1

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

Description

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown 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 20, 2024

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