rs200015017

chr6-38851567-T-G

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.5364-5T>G variant causes a splice region, splice polypyrimidine tract, intron change. The variant allele was found at a frequency of 0.000891 in 1,577,762 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00077 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00090 (12 hom.)
• Consequence: DNAH8 NM_001206927.2 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.2163
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.80

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=-0.53).
• BP6: Variant 6-38851567-T-G is Benign according to our data. Variant chr6-38851567-T-G is described in ClinVar as [Benign]. Clinvar id is 525562.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000775 (118/152330) while in subpopulation SAS AF= 0.0087 (42/4828). AF 95% confidence interval is 0.00661. There are 0 homozygotes in gnomad4. There are 69 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH8	NM_001206927.2	c.5364-5T>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000327475.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH8	ENST00000327475.11	c.5364-5T>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5	NM_001206927.2	P2
DNAH8	ENST00000359357.7	c.4713-5T>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		2		A2
DNAH8	ENST00000449981.6	c.5364-5T>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.000775 AC: 118 AN: 152212 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00118

Gnomad ASJ AF: 0.00403

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00869

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000588

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.00130 AC: 302 AN: 233062 Hom.: 3 AF XY: 0.00160 AC XY: 201 AN XY: 125858

Gnomad AFR exome AF: 0.0000629

Gnomad AMR exome AF: 0.000347

Gnomad ASJ exome AF: 0.00312

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00774

Gnomad FIN exome AF: 0.0000468

Gnomad NFE exome AF: 0.000532

Gnomad OTH exome AF: 0.000525

GnomAD4 exome AF: 0.000904 AC: 1288 AN: 1425432 Hom.: 12 Cov.: 26 AF XY: 0.00116 AC XY: 820 AN XY: 709658

Gnomad4 AFR exome AF: 0.0000630

Gnomad4 AMR exome AF: 0.000335

Gnomad4 ASJ exome AF: 0.00304

Gnomad4 EAS exome AF: 0.0000254

Gnomad4 SAS exome AF: 0.00881

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000351

Gnomad4 OTH exome AF: 0.00130

GnomAD4 genome AF: 0.000775 AC: 118 AN: 152330 Hom.: 0 Cov.: 32 AF XY: 0.000926 AC XY: 69 AN XY: 74492

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00118

Gnomad4 ASJ AF: 0.00403

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00870

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000588

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.000779 Hom.: 0

Bravo AF: 0.000669

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.000873

EpiControl AF: 0.000593

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 24, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
Cadd	Benign	16
Dann	Benign	0.58

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.22
dbscSNV1_RF	Benign	0.37
SpliceAI score (max)		0.050		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: rs200015017; hg19: chr6-38819343;