NM_001099697.2:c.2540T>C

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001099697.2(RSPH10B2):​c.2540T>C​(p.Leu847Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 7)
Exomes 𝑓: 0.0000088 ( 3 hom. )
Failed GnomAD Quality Control

Consequence

RSPH10B2
NM_001099697.2 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0230

Publications

0 publications found
Variant links:
Genes affected
RSPH10B2 (HGNC:34385): (radial spoke head 10 homolog B2) This gene encodes a protein component of the radial spoke head in flagella and motile cilia. Eukaryotic flagella and motile cilia share a common 9 + 2 structure, in which nine peripheral microtubule doublets (MTDs) surround a central-pair of microtubules (CP), with radial spokes connecting the MTDs to the CP. The radial spoke is a multi-protein complex that works as a mechanochemical transducer between the CP and the MTDs. The radial spoke contributes to the regulation of the activity of dynein motors, and thus to flagellar motility. PMID: 22754630 provides a good review of radial spokes. [provided by RefSeq, Jul 2017]
CCZ1B (HGNC:21717): (CCZ1 homolog B, vacuolar protein trafficking and biogenesis associated) Enables guanyl-nucleotide exchange factor activity. Predicted to be involved in vesicle-mediated transport. Located in intracellular membrane-bounded organelle. Part of Mon1-Ccz1 complex. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.05795926).
BP6
Variant 7-6798470-T-C is Benign according to our data. Variant chr7-6798470-T-C is described in CliVar as Likely_benign. Clinvar id is 2258428.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-6798470-T-C is described in CliVar as Likely_benign. Clinvar id is 2258428.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-6798470-T-C is described in CliVar as Likely_benign. Clinvar id is 2258428.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-6798470-T-C is described in CliVar as Likely_benign. Clinvar id is 2258428.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-6798470-T-C is described in CliVar as Likely_benign. Clinvar id is 2258428.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-6798470-T-C is described in CliVar as Likely_benign. Clinvar id is 2258428.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-6798470-T-C is described in CliVar as Likely_benign. Clinvar id is 2258428.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-6798470-T-C is described in CliVar as Likely_benign. Clinvar id is 2258428.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-6798470-T-C is described in CliVar as Likely_benign. Clinvar id is 2258428.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-6798470-T-C is described in CliVar as Likely_benign. Clinvar id is 2258428.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RSPH10B2NM_001099697.2 linkc.2540T>C p.Leu847Pro missense_variant Exon 21 of 21 ENST00000404077.6 NP_001093167.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RSPH10B2ENST00000404077.6 linkc.2540T>C p.Leu847Pro missense_variant Exon 21 of 21 1 NM_001099697.2 ENSP00000386102.1 B2RC85-1

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
0
AN:
64684
Hom.:
0
Cov.:
7
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.00000877
AC:
9
AN:
1026732
Hom.:
3
Cov.:
17
AF XY:
0.00000591
AC XY:
3
AN XY:
507302
show subpopulations
African (AFR)
AF:
0.0000528
AC:
1
AN:
18924
American (AMR)
AF:
0.00
AC:
0
AN:
24372
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
18002
East Asian (EAS)
AF:
0.00
AC:
0
AN:
24162
South Asian (SAS)
AF:
0.00
AC:
0
AN:
35326
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
42118
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
3910
European-Non Finnish (NFE)
AF:
0.00000978
AC:
8
AN:
817840
Other (OTH)
AF:
0.00
AC:
0
AN:
42078
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.458
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Data not reliable, filtered out with message: AC0;AS_VQSR
AF:
0.00
AC:
0
AN:
64684
Hom.:
0
Cov.:
7
AF XY:
0.00
AC XY:
0
AN XY:
29590
African (AFR)
AF:
0.00
AC:
0
AN:
12904
American (AMR)
AF:
0.00
AC:
0
AN:
5128
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
1666
East Asian (EAS)
AF:
0.00
AC:
0
AN:
1450
South Asian (SAS)
AF:
0.00
AC:
0
AN:
714
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
4184
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
126
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
37280
Other (OTH)
AF:
0.00
AC:
0
AN:
786
Alfa
AF:
0.00
Hom.:
0

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Oct 29, 2021
Ambry Genetics
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.050
BayesDel_addAF
Benign
-0.35
T
BayesDel_noAF
Benign
-0.74
CADD
Benign
3.7
DANN
Benign
0.80
DEOGEN2
Benign
0.00036
T;T;T
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.00053
N
LIST_S2
Benign
0.31
.;.;T
M_CAP
Benign
0.0022
T
MetaRNN
Benign
0.058
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.10
N;N;N
PhyloP100
-0.023
PrimateAI
Benign
0.37
T
PROVEAN
Benign
1.6
N;N;N
REVEL
Benign
0.067
Sift
Benign
0.42
T;T;T
Sift4G
Benign
0.43
T;T;T
Polyphen
0.0
B;B;B
Vest4
0.067
MVP
0.081
ClinPred
0.040
T
GERP RS
1.8
Varity_R
0.033
gMVP
0.037
Mutation Taster
=96/4
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs1782696292; hg19: chr7-6838101; API