Variant 6-38909647-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2BP4_StrongBP6_ModerateBS1

The NM_001206927.2(DNAH8):c.9643A>T(p.Asn3215Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000229 in 1,614,160 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0012 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

DNAH8
NM_001206927.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.397

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:

DNAH8-AS1 (HGNC:):

DNAH8-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.008991748).

BP6

Variant 6-38909647-A-T is Benign according to our data. Variant chr6-38909647-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 414420.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00125 (190/152330) while in subpopulation AFR AF= 0.00435 (181/41576). AF 95% confidence interval is 0.00383. There are 1 homozygotes in gnomad4. There are 92 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH8	NM_001206927.2 linkuse as main transcript	c.9643A>T	p.Asn3215Tyr	missense_variant	65/93	ENST00000327475.11	NP_001193856.1
DNAH8-AS1	NR_038401.1 linkuse as main transcript	n.783-1810T>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH8	ENST00000327475.11 linkuse as main transcript	c.9643A>T	p.Asn3215Tyr	missense_variant	65/93	5	NM_001206927.2	ENSP00000333363	P2
DNAH8	ENST00000359357.7 linkuse as main transcript	c.8992A>T	p.Asn2998Tyr	missense_variant	63/91	2		ENSP00000352312	A2	Q96JB1-1
DNAH8	ENST00000449981.6 linkuse as main transcript	c.9643A>T	p.Asn3215Tyr	missense_variant	64/82	5		ENSP00000415331

Frequencies

GnomAD3 genomes

AF:

0.00125

AC:

191

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00439

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000275

AC:

AN:

251180

Hom.:

AF XY:

0.000177

AC XY:

AN XY:

135736

show subpopulations

Gnomad AFR exome

AF:

0.00381

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000122

AC:

179

AN:

1461830

Hom.:

Cov.:

AF XY:

0.000103

AC XY:

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.00451

Gnomad4 AMR exome

AF:

0.000134

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000315

GnomAD4 genome

AF:

0.00125

AC:

190

AN:

152330

Hom.:

Cov.:

AF XY:

0.00124

AC XY:

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.00435

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000178

Hom.:

Bravo

AF:

0.00136

ESP6500AA

AF:

0.00363

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000346

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.083

T;T;T

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.27

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.70

T;T;T

M_CAP

Benign

0.019

MetaRNN

Benign

0.0090

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

.;.;L

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.28

PROVEAN

Uncertain

-4.3

.;D;D

REVEL

Benign

0.055

Sift

Uncertain

0.0060

.;D;D

Polyphen

0.63

.;.;P

Vest4

0.47

MVP

0.84

MPC

0.20

ClinPred

0.049

GERP RS

3.2

Varity_R

0.23

gMVP

0.27

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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