rs3737095

chr6-38989995-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001206927.2(DNAH8):c.13054-17T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.42 in 1,483,332 control chromosomes in the GnomAD database, including 134,529 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.40 (12544 hom., cov: 32)
  • Exomes 𝑓: 0.42 (121985 hom.)
• Consequence: DNAH8 NM_001206927.2 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 3.48

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 6-38989995-T-C is Benign according to our data. Variant chr6-38989995-T-C is described in ClinVar as [Benign]. Clinvar id is 257628.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH8	NM_001206927.2	c.13054-17T>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000327475.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH8	ENST00000327475.11	c.13054-17T>C		splice_polypyrimidine_tract_variant, intron_variant		5	NM_001206927.2	P2
DNAH8	ENST00000359357.7	c.12403-17T>C		splice_polypyrimidine_tract_variant, intron_variant		2		A2

Frequencies

GnomAD3 genomes AF: 0.400 AC: 60697 AN: 151868 Hom.: 12533 Cov.: 32

Gnomad AFR AF: 0.336

Gnomad AMI AF: 0.466

Gnomad AMR AF: 0.381

Gnomad ASJ AF: 0.390

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.445

Gnomad MID AF: 0.404

Gnomad NFE AF: 0.454

Gnomad OTH AF: 0.400

GnomAD3 exomes AF: 0.381 AC: 79008 AN: 207216 Hom.: 15859 AF XY: 0.383 AC XY: 43039 AN XY: 112450

Gnomad AFR exome AF: 0.318

Gnomad AMR exome AF: 0.307

Gnomad ASJ exome AF: 0.373

Gnomad EAS exome AF: 0.238

Gnomad SAS exome AF: 0.287

Gnomad FIN exome AF: 0.432

Gnomad NFE exome AF: 0.442

Gnomad OTH exome AF: 0.405

GnomAD4 exome AF: 0.422 AC: 562276 AN: 1331346 Hom.: 121985 Cov.: 20 AF XY: 0.420 AC XY: 278063 AN XY: 662422

Gnomad4 AFR exome AF: 0.313

Gnomad4 AMR exome AF: 0.323

Gnomad4 ASJ exome AF: 0.384

Gnomad4 EAS exome AF: 0.233

Gnomad4 SAS exome AF: 0.288

Gnomad4 FIN exome AF: 0.441

Gnomad4 NFE exome AF: 0.446

Gnomad4 OTH exome AF: 0.416

GnomAD4 genome AF: 0.400 AC: 60742 AN: 151986 Hom.: 12544 Cov.: 32 AF XY: 0.396 AC XY: 29446 AN XY: 74304

Gnomad4 AFR AF: 0.336

Gnomad4 AMR AF: 0.380

Gnomad4 ASJ AF: 0.390

Gnomad4 EAS AF: 0.254

Gnomad4 SAS AF: 0.296

Gnomad4 FIN AF: 0.445

Gnomad4 NFE AF: 0.454

Gnomad4 OTH AF: 0.400

Alfa AF: 0.413 Hom.: 2917

Bravo AF: 0.392

Asia WGS AF: 0.299 AC: 1040 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Primary ciliary dyskinesia Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
Cadd	Benign	14
Dann	Benign	0.87

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs3737095; hg19: chr6-38957771; COSMIC: COSV59469826;