7-6779690-C-T

Variant names:

• chr7-6779690-C-T
• rs200167275
• NM_001099697.2:c.1495C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001099697.2(RSPH10B2):​c.1495C>T​(p.His499Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.016 (147 hom., cov: 12)
  • Exomes 𝑓: 0.019 (765 hom.)
• Consequence: RSPH10B2 NM_001099697.2 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.951

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]

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.003009528).
• BP6: Variant 7-6779690-C-T is Benign according to our data. Variant chr7-6779690-C-T is described in ClinVar as [Benign]. Clinvar id is 770736.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0163 (1571/96094) while in subpopulation NFE AF = 0.0254 (1211/47606). AF 95% confidence interval is 0.0242. There are 147 homozygotes in GnomAd4. There are 664 alleles in the male GnomAd4 subpopulation. Median coverage is 12. This position FAILED quality control check.
• BS2: High Homozygotes in GnomAd4 at 147 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RSPH10B2	NM_001099697.2	c.1495C>T	p.His499Tyr	missense_variant	Exon 13 of 21	ENST00000404077.6	NP_001093167.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RSPH10B2	ENST00000404077.6	c.1495C>T	p.His499Tyr	missense_variant	Exon 13 of 21	1	NM_001099697.2	ENSP00000386102.1

Frequencies

GnomAD3 genomes AF: 0.0164 AC: 1574 AN: 96016 Hom.: 148 Cov.: 12

Gnomad AFR AF: 0.00546

Gnomad AMI AF: 0.00977

Gnomad AMR AF: 0.0131

Gnomad ASJ AF: 0.0227

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00535

Gnomad FIN AF: 0.00460

Gnomad MID AF: 0.0159

Gnomad NFE AF: 0.0255

Gnomad OTH AF: 0.0157

GnomAD2 exomes AF: 0.0142 AC: 585 AN: 41294 AF XY: 0.0140

Gnomad AFR exome AF: 0.00375

Gnomad AMR exome AF: 0.0118

Gnomad ASJ exome AF: 0.0164

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00518

Gnomad NFE exome AF: 0.0258

Gnomad OTH exome AF: 0.00843

GnomAD4 exome AF: 0.0193 AC: 6162 AN: 319248 Hom.: 765 Cov.: 0 AF XY: 0.0188 AC XY: 3149 AN XY: 167586

Gnomad4 AFR exome AF: 0.00536 AC: 46 AN: 8588

Gnomad4 AMR exome AF: 0.0102 AC: 111 AN: 10922

Gnomad4 ASJ exome AF: 0.0205 AC: 176 AN: 8586

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 17626

Gnomad4 SAS exome AF: 0.00550 AC: 150 AN: 27266

Gnomad4 FIN exome AF: 0.00674 AC: 228 AN: 33838

Gnomad4 NFE exome AF: 0.0265 AC: 5134 AN: 193968

Gnomad4 Remaining exome AF: 0.0171 AC: 293 AN: 17152

GnomAD4 genome AF: 0.0163 AC: 1571 AN: 96094 Hom.: 147 Cov.: 12 AF XY: 0.0148 AC XY: 664 AN XY: 45010

Gnomad4 AFR AF: 0.00544 AC: 0.00543651 AN: 0.00543651

Gnomad4 AMR AF: 0.0129 AC: 0.0129064 AN: 0.0129064

Gnomad4 ASJ AF: 0.0227 AC: 0.0227078 AN: 0.0227078

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.00535 AC: 0.00535077 AN: 0.00535077

Gnomad4 FIN AF: 0.00460 AC: 0.004597 AN: 0.004597

Gnomad4 NFE AF: 0.0254 AC: 0.025438 AN: 0.025438

Gnomad4 OTH AF: 0.0156 AC: 0.0155709 AN: 0.0155709

Alfa AF: 0.0164 Hom.: 41

ExAC AF: 0.0116 AC: 884

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Sep 21, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	16
DANN	Benign	0.30
DEOGEN2	Benign	0.0058	T;T;T
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.48	.;.;T
MetaRNN	Benign	0.0030	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.20	N;N;N
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-1.0	N;N;N
REVEL	Benign	0.11
Sift	Benign	1.0	T;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0080	B;B;B
Vest4		0.069
ClinPred		0.0059	T
GERP RS		3.6
Varity_R		0.063
gMVP		0.17
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs200167275; hg19: chr7-6819321; COSMIC: COSV99032680; COSMIC: COSV99032680;