rs112605623

chr6-38884004-G-Achr6-38884004-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001206927.2(DNAH8):c.8259+6G>A variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0012 in 1,528,264 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0060 (7 hom., cov: 32)
  • Exomes 𝑓: 0.00067 (9 hom.)
• Consequence: DNAH8 NM_001206927.2 splice_donor_region, intron
• Scores: Splicing: ADA: 0.00002157
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.271

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 6-38884004-G-A is Benign according to our data. Variant chr6-38884004-G-A is described in ClinVar as [Benign]. Clinvar id is 238656.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00597 (907/151804) while in subpopulation AFR AF= 0.0192 (797/41430). AF 95% confidence interval is 0.0181. There are 7 homozygotes in gnomad4. There are 426 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH8	NM_001206927.2	c.8259+6G>A		splice_donor_region_variant, intron_variant		ENST00000327475.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH8	ENST00000327475.11	c.8259+6G>A		splice_donor_region_variant, intron_variant		5	NM_001206927.2	P2
DNAH8	ENST00000359357.7	c.7608+6G>A		splice_donor_region_variant, intron_variant		2		A2
DNAH8	ENST00000449981.6	c.8259+6G>A		splice_donor_region_variant, intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.00599 AC: 908 AN: 151690 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.0193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00486

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: 0.000339

Gnomad OTH AF: 0.00575

GnomAD3 exomes AF: 0.00149 AC: 331 AN: 221438 Hom.: 2 AF XY: 0.00112 AC XY: 135 AN XY: 120710

Gnomad AFR exome AF: 0.0196

Gnomad AMR exome AF: 0.00139

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000384

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000117

Gnomad OTH exome AF: 0.00137

GnomAD4 exome AF: 0.000668 AC: 920 AN: 1376460 Hom.: 9 Cov.: 28 AF XY: 0.000625 AC XY: 427 AN XY: 683040

Gnomad4 AFR exome AF: 0.0198

Gnomad4 AMR exome AF: 0.00189

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000422

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000128

Gnomad4 OTH exome AF: 0.00152

GnomAD4 genome AF: 0.00597 AC: 907 AN: 151804 Hom.: 7 Cov.: 32 AF XY: 0.00574 AC XY: 426 AN XY: 74224

Gnomad4 AFR AF: 0.0192

Gnomad4 AMR AF: 0.00486

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000339

Gnomad4 OTH AF: 0.00569

Alfa AF: 0.00184 Hom.: 0

Bravo AF: 0.00680

Asia WGS AF: 0.00173 AC: 6 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Primary ciliary dyskinesia Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 26, 2024

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.62
Dann	Benign	0.25

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000022
dbscSNV1_RF	Benign	0.0020
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

Other links and lift over

dbSNP: rs112605623; hg19: chr6-38851780;