dbSNP rs114095356: DNAH8:p.Thr4323Thr (chr6-38984223-G-A) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001206927.2(DNAH8):c.12969G>A(p.Thr4323Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000503 in 1,592,166 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0023 ( 4 hom., cov: 32)

Exomes 𝑓: 0.00032 ( 0 hom. )

Consequence

DNAH8
NM_001206927.2 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -3.74

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 6-38984223-G-A is Benign according to our data. Variant chr6-38984223-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 414427.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.74 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00227 (346/152208) while in subpopulation AFR AF= 0.00742 (308/41510). AF 95% confidence interval is 0.00674. There are 4 homozygotes in gnomad4. There are 161 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH8	NM_001206927.2 link	c.12969G>A	p.Thr4323Thr	synonymous_variant	Exon 87 of 93	ENST00000327475.11	NP_001193856.1	Q96JB1Q8IU65A0A075B6F3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH8	ENST00000327475.11 link	c.12969G>A	p.Thr4323Thr	synonymous_variant	Exon 87 of 93	5	NM_001206927.2	ENSP00000333363.7		A0A075B6F3
DNAH8	ENST00000359357.7 link	c.12318G>A	p.Thr4106Thr	synonymous_variant	Exon 85 of 91	2		ENSP00000352312.3		Q96JB1-1

Frequencies

GnomAD3 genomes

AF:

0.00218

AC:

331

AN:

152088

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00708

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00138

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.000760

AC:

190

AN:

249928

Hom.:

AF XY:

0.000548

AC XY:

AN XY:

135090

show subpopulations

Gnomad AFR exome

AF:

0.00660

Gnomad AMR exome

AF:

0.00146

Gnomad ASJ exome

AF:

0.0000996

Gnomad EAS exome

AF:

0.0000546

Gnomad SAS exome

AF:

0.000297

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000124

Gnomad OTH exome

AF:

0.00132

GnomAD4 exome

AF:

0.000316

AC:

455

AN:

1439958

Hom.:

Cov.:

AF XY:

0.000322

AC XY:

231

AN XY:

717554

show subpopulations

Gnomad4 AFR exome

AF:

0.00769

Gnomad4 AMR exome

AF:

0.00139

Gnomad4 ASJ exome

AF:

0.0000385

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.000175

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000705

Gnomad4 OTH exome

AF:

0.000553

GnomAD4 genome

AF:

0.00227

AC:

346

AN:

152208

Hom.:

Cov.:

AF XY:

0.00216

AC XY:

161

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.00742

Gnomad4 AMR

AF:

0.00137

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.00236

Alfa

AF:

0.00112

Hom.:

Bravo

AF:

0.00261

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000178

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia

Benign:1

Jan 21, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Aug 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

DNAH8: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.023

DANN

Benign

0.46

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