Variant chr6-38915224-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_001206927.2(DNAH8):c.9987C>T(p.Ser3329=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00267 in 1,604,264 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0022 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0027 ( 13 hom. )

Consequence

DNAH8
NM_001206927.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.352

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.3).

BP6

Variant 6-38915224-C-T is Benign according to our data. Variant chr6-38915224-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 414400.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.352 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00225 (342/152208) while in subpopulation NFE AF= 0.00325 (221/68016). AF 95% confidence interval is 0.0029. There are 0 homozygotes in gnomad4. There are 170 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH8	NM_001206927.2 linkuse as main transcript	c.9987C>T	p.Ser3329=	synonymous_variant	68/93	ENST00000327475.11
DNAH8-AS1	NR_038401.1 linkuse as main transcript	n.783-7387G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH8	ENST00000327475.11 linkuse as main transcript	c.9987C>T	p.Ser3329=	synonymous_variant	68/93	5	NM_001206927.2	P2
DNAH8	ENST00000359357.7 linkuse as main transcript	c.9336C>T	p.Ser3112=	synonymous_variant	66/91	2		A2	Q96JB1-1
DNAH8	ENST00000449981.6 linkuse as main transcript	c.9987C>T	p.Ser3329=	synonymous_variant	67/82	5

Frequencies

GnomAD3 genomes

AF:

0.00225

AC:

342

AN:

152090

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000531

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00746

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00325

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00329

AC:

797

AN:

242030

Hom.:

AF XY:

0.00346

AC XY:

453

AN XY:

131076

show subpopulations

Gnomad AFR exome

AF:

0.000445

Gnomad AMR exome

AF:

0.000412

Gnomad ASJ exome

AF:

0.00101

Gnomad EAS exome

AF:

0.0000571

Gnomad SAS exome

AF:

0.00151

Gnomad FIN exome

AF:

0.00878

Gnomad NFE exome

AF:

0.00465

Gnomad OTH exome

AF:

0.00291

GnomAD4 exome

AF:

0.00272

AC:

3945

AN:

1452056

Hom.:

Cov.:

AF XY:

0.00268

AC XY:

1934

AN XY:

722300

show subpopulations

Gnomad4 AFR exome

AF:

0.000305

Gnomad4 AMR exome

AF:

0.000354

Gnomad4 ASJ exome

AF:

0.000694

Gnomad4 EAS exome

AF:

0.0000256

Gnomad4 SAS exome

AF:

0.00182

Gnomad4 FIN exome

AF:

0.0101

Gnomad4 NFE exome

AF:

0.00277

Gnomad4 OTH exome

AF:

0.00228

GnomAD4 genome

AF:

0.00225

AC:

342

AN:

152208

Hom.:

Cov.:

AF XY:

0.00228

AC XY:

170

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.000530

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00746

Gnomad4 NFE

AF:

0.00325

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00309

Hom.:

Bravo

AF:

0.00174

Asia WGS

AF:

0.00144

AC:

AN:

3476

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

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2024

DNAH8: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.30

CADD

Benign

6.2

DANN

Benign

0.74

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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