Genetic Variant NM_001206927.2:c.1050C>T (chr6-38737906-C-T) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001206927.2(DNAH8):c.1050C>T(p.Ala350Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0192 in 1,605,436 control chromosomes in the GnomAD database, including 755 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 43 hom., cov: 32)

Exomes 𝑓: 0.020 ( 712 hom. )

Consequence

DNAH8
NM_001206927.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.54

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 6-38737906-C-T is Benign according to our data. Variant chr6-38737906-C-T is described in ClinVar as [Benign]. Clinvar id is 414417.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.54 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0962 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH8	NM_001206927.2 link	c.1050C>T	p.Ala350Ala	synonymous_variant	Exon 7 of 93	ENST00000327475.11	NP_001193856.1	Q96JB1Q8IU65A0A075B6F3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DNAH8	ENST00000327475.11 link	c.1050C>T	p.Ala350Ala	synonymous_variant	Exon 7 of 93	5	NM_001206927.2	ENSP00000333363.7	A0A075B6F3
DNAH8	ENST00000359357.7 link	c.399C>T	p.Ala133Ala	synonymous_variant	Exon 5 of 91	2		ENSP00000352312.3	Q96JB1-1
DNAH8	ENST00000449981.6 link	c.1050C>T	p.Ala350Ala	synonymous_variant	Exon 6 of 82	5		ENSP00000415331.2	H0Y7V4

Frequencies

GnomAD3 genomes

AF:

0.0149

AC:

2259

AN:

152066

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00355

Gnomad AMI

AF:

0.0263

Gnomad AMR

AF:

0.0111

Gnomad ASJ

AF:

0.0112

Gnomad EAS

AF:

0.0535

Gnomad SAS

AF:

0.105

Gnomad FIN

AF:

0.0176

Gnomad MID

AF:

0.0159

Gnomad NFE

AF:

0.0130

Gnomad OTH

AF:

0.0110

GnomAD3 exomes

AF:

0.0281

AC:

6820

AN:

242306

Hom.:

213

AF XY:

0.0315

AC XY:

4141

AN XY:

131528

show subpopulations

Gnomad AFR exome

AF:

0.00346

Gnomad AMR exome

AF:

0.0194

Gnomad ASJ exome

AF:

0.0131

Gnomad EAS exome

AF:

0.0499

Gnomad SAS exome

AF:

0.101

Gnomad FIN exome

AF:

0.0162

Gnomad NFE exome

AF:

0.0154

Gnomad OTH exome

AF:

0.0184

GnomAD4 exome

AF:

0.0196

AC:

28541

AN:

1453252

Hom.:

712

Cov.:

AF XY:

0.0221

AC XY:

15998

AN XY:

723212

show subpopulations

Gnomad4 AFR exome

AF:

0.00287

Gnomad4 AMR exome

AF:

0.0181

Gnomad4 ASJ exome

AF:

0.0118

Gnomad4 EAS exome

AF:

0.0432

Gnomad4 SAS exome

AF:

0.101

Gnomad4 FIN exome

AF:

0.0159

Gnomad4 NFE exome

AF:

0.0133

Gnomad4 OTH exome

AF:

0.0218

GnomAD4 genome

AF:

0.0148

AC:

2251

AN:

152184

Hom.:

Cov.:

AF XY:

0.0164

AC XY:

1217

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.00354

Gnomad4 AMR

AF:

0.0111

Gnomad4 ASJ

AF:

0.0112

Gnomad4 EAS

AF:

0.0530

Gnomad4 SAS

AF:

0.104

Gnomad4 FIN

AF:

0.0176

Gnomad4 NFE

AF:

0.0130

Gnomad4 OTH

AF:

0.0109

Alfa

AF:

0.0128

Hom.:

Bravo

AF:

0.0123

Asia WGS

AF:

0.0780

AC:

271

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

May 04, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.67

DANN

Benign

0.43

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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