rs150857304

chr6-38915224-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS1

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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.352

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-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -15 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH8	NM_001206927.2	c.9987C>T	p.Ser3329=	synonymous_variant	68/93	ENST00000327475.11
DNAH8-AS1	NR_038401.1	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	c.9987C>T	p.Ser3329=	synonymous_variant	68/93	5	NM_001206927.2	P2
DNAH8	ENST00000359357.7	c.9336C>T	p.Ser3112=	synonymous_variant	66/91	2		A2
DNAH8	ENST00000449981.6	c.9987C>T	p.Ser3329=	synonymous_variant	67/82	5

Frequencies

GnomAD3 genomes AF: 0.00225 AC: 342 AN: 152090 Hom.: 0 Cov.: 32

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.: 1 AF XY: 0.00346 AC XY: 453 AN XY: 131076

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.: 13 Cov.: 31 AF XY: 0.00268 AC XY: 1934 AN XY: 722300

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.: 0 Cov.: 32 AF XY: 0.00228 AC XY: 170 AN XY: 74406

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.: 1

Bravo AF: 0.00174

Asia WGS AF: 0.00144 AC: 5 AN: 3476

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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

Other links and lift over

dbSNP: rs150857304; hg19: chr6-38883000;