Variant rs61758417 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001206927.2(DNAH8):c.7171G>T(p.Ala2391Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0111 in 1,614,060 control chromosomes in the GnomAD database, including 909 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.010 ( 91 hom., cov: 33)

Exomes 𝑓: 0.011 ( 818 hom. )

Consequence

DNAH8
NM_001206927.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 9.92

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=0.0022349358).

BP6

Variant 6-38872716-G-T is Benign according to our data. Variant chr6-38872716-G-T is described in ClinVar as [Benign]. Clinvar id is 414424.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH8	NM_001206927.2 linkuse as main transcript	c.7171G>T	p.Ala2391Ser	missense_variant	50/93	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.7171G>T	p.Ala2391Ser	missense_variant	50/93	5	NM_001206927.2	ENSP00000333363	P2
DNAH8	ENST00000359357.7 linkuse as main transcript	c.6520G>T	p.Ala2174Ser	missense_variant	48/91	2		ENSP00000352312	A2	Q96JB1-1
DNAH8	ENST00000449981.6 linkuse as main transcript	c.7171G>T	p.Ala2391Ser	missense_variant	49/82	5		ENSP00000415331

Frequencies

GnomAD3 genomes

AF:

0.0104

AC:

1576

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00205

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00727

Gnomad ASJ

AF:

0.00490

Gnomad EAS

AF:

0.148

Gnomad SAS

AF:

0.0967

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.00160

Gnomad OTH

AF:

0.00717

GnomAD3 exomes

AF:

0.0250

AC:

6272

AN:

251102

Hom.:

327

AF XY:

0.0280

AC XY:

3798

AN XY:

135686

show subpopulations

Gnomad AFR exome

AF:

0.00166

Gnomad AMR exome

AF:

0.0158

Gnomad ASJ exome

AF:

0.00437

Gnomad EAS exome

AF:

0.142

Gnomad SAS exome

AF:

0.0900

Gnomad FIN exome

AF:

0.000693

Gnomad NFE exome

AF:

0.00174

Gnomad OTH exome

AF:

0.0145

GnomAD4 exome

AF:

0.0112

AC:

16393

AN:

1461788

Hom.:

818

Cov.:

AF XY:

0.0136

AC XY:

9919

AN XY:

727208

show subpopulations

Gnomad4 AFR exome

AF:

0.00120

Gnomad4 AMR exome

AF:

0.0143

Gnomad4 ASJ exome

AF:

0.00448

Gnomad4 EAS exome

AF:

0.135

Gnomad4 SAS exome

AF:

0.0888

Gnomad4 FIN exome

AF:

0.000749

Gnomad4 NFE exome

AF:

0.00132

Gnomad4 OTH exome

AF:

0.0167

GnomAD4 genome

AF:

0.0103

AC:

1568

AN:

152272

Hom.:

Cov.:

AF XY:

0.0127

AC XY:

948

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.00204

Gnomad4 AMR

AF:

0.00726

Gnomad4 ASJ

AF:

0.00490

Gnomad4 EAS

AF:

0.147

Gnomad4 SAS

AF:

0.0960

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.00160

Gnomad4 OTH

AF:

0.00710

Alfa

AF:

0.00878

Hom.:

144

Bravo

AF:

0.00951

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00389

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00128

AC:

ExAC

AF:

0.0257

AC:

3116

Asia WGS

AF:

0.104

AC:

359

AN:

3476

EpiCase

AF:

0.00267

EpiControl

AF:

0.00285

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 25, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 04, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.071

T;T;T

Eigen

Pathogenic

0.77

Eigen_PC

Pathogenic

0.78

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.97

D;D;D

MetaRNN

Benign

0.0022

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.4

.;.;L

MutationTaster

Benign

6.3e-10

P;P;P

PrimateAI

Uncertain

0.68

PROVEAN

Uncertain

-2.6

.;D;D

REVEL

Uncertain

0.31

Sift

Uncertain

0.023

.;D;D

Polyphen

0.99

.;.;D

Vest4

0.48

MPC

0.47

ClinPred

0.026

GERP RS

5.6

Varity_R

0.35

gMVP

0.28

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

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