rs150571615

Positions:

chr6-38896194-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001206927.2(DNAH8):c.8909C>T(p.Ser2970Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000297 in 1,613,978 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0015 ( 3 hom., cov: 32)

Exomes 𝑓: 0.00018 ( 0 hom. )

Consequence

DNAH8
NM_001206927.2 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.41

Variant links:

Genes affected

DNAH8 (HGNC:2952): (dynein axonemal heavy chain 8) The protein encoded by this gene is a heavy chain of an axonemal dynein involved in sperm and respiratory cilia motility. Axonemal dyneins generate force through hydrolysis of ATP and binding to microtubules. [provided by RefSeq, Jan 2012]

DNAH8 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0032912493).

BP6

Variant 6-38896194-C-T is Benign according to our data. Variant chr6-38896194-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 414375.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00146 (223/152242) while in subpopulation AFR AF= 0.0052 (216/41540). AF 95% confidence interval is 0.00463. There are 3 homozygotes in gnomad4. There are 115 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH8	NM_001206927.2 linkuse as main transcript	c.8909C>T	p.Ser2970Phe	missense_variant	60/93	ENST00000327475.11	NP_001193856.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH8	ENST00000327475.11 linkuse as main transcript	c.8909C>T	p.Ser2970Phe	missense_variant	60/93	5	NM_001206927.2	ENSP00000333363	P2
DNAH8	ENST00000359357.7 linkuse as main transcript	c.8258C>T	p.Ser2753Phe	missense_variant	58/91	2		ENSP00000352312	A2	Q96JB1-1
DNAH8	ENST00000449981.6 linkuse as main transcript	c.8909C>T	p.Ser2970Phe	missense_variant	59/82	5		ENSP00000415331

Frequencies

GnomAD3 genomes

AF:

0.00145

AC:

221

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00517

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

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:

0.00191

GnomAD3 exomes

AF:

0.000339

AC:

AN:

250936

Hom.:

AF XY:

0.000192

AC XY:

AN XY:

135596

show subpopulations

Gnomad AFR exome

AF:

0.00412

Gnomad AMR exome

AF:

0.000463

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000176

AC:

257

AN:

1461736

Hom.:

Cov.:

AF XY:

0.000144

AC XY:

105

AN XY:

727162

show subpopulations

Gnomad4 AFR exome

AF:

0.00565

Gnomad4 AMR exome

AF:

0.000559

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000989

Gnomad4 OTH exome

AF:

0.000497

GnomAD4 genome

AF:

0.00146

AC:

223

AN:

152242

Hom.:

Cov.:

AF XY:

0.00154

AC XY:

115

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.00520

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.000287

Hom.:

Bravo

AF:

0.00161

ESP6500AA

AF:

0.00522

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000395

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

DNAH8-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 10, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Primary ciliary dyskinesia

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.70

CADD

Benign

DANN

Benign

0.47

DEOGEN2

Benign

0.025

T;T;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.92

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.85

D;D;D

M_CAP

Benign

0.0091

MetaRNN

Benign

0.0033

T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

-0.40

.;.;N

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.9

.;N;N

REVEL

Benign

0.072

Sift

Benign

0.78

.;T;T

Polyphen

0.0

.;.;B

Vest4

0.16

MVP

0.32

MPC

0.13

ClinPred

0.0060

GERP RS

1.1

Varity_R

0.057

gMVP

0.25

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over