rs11291395

chr6-38917234-TA-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001206927.2(DNAH8):c.10141-4del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.50 (20282 hom., cov: 0)
  • Exomes 𝑓: 0.43 (139758 hom.)
• Consequence: DNAH8 NM_001206927.2 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.492

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 -16 ACMG points.

• BP6: Variant 6-38917234-TA-T is Benign according to our data. Variant chr6-38917234-TA-T is described in ClinVar as [Benign]. Clinvar id is 257626.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-38917234-TA-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.682 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH8	NM_001206927.2	c.10141-4del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000327475.11
DNAH8-AS1	NR_038401.1	n.782+5850del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH8	ENST00000327475.11	c.10141-4del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5	NM_001206927.2	P2
DNAH8	ENST00000359357.7	c.9490-4del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		2		A2
DNAH8	ENST00000449981.6	c.10141-4del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.501 AC: 76043 AN: 151826 Hom.: 20259 Cov.: 0

Gnomad AFR AF: 0.688

Gnomad AMI AF: 0.317

Gnomad AMR AF: 0.414

Gnomad ASJ AF: 0.420

Gnomad EAS AF: 0.495

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.456

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.436

Gnomad OTH AF: 0.469

GnomAD3 exomes AF: 0.427 AC: 104301 AN: 244146 Hom.: 23633 AF XY: 0.418 AC XY: 55085 AN XY: 131822

Gnomad AFR exome AF: 0.690

Gnomad AMR exome AF: 0.330

Gnomad ASJ exome AF: 0.429

Gnomad EAS exome AF: 0.524

Gnomad SAS exome AF: 0.284

Gnomad FIN exome AF: 0.451

Gnomad NFE exome AF: 0.436

Gnomad OTH exome AF: 0.420

GnomAD4 exome AF: 0.434 AC: 628147 AN: 1447302 Hom.: 139758 Cov.: 0 AF XY: 0.430 AC XY: 309106 AN XY: 719618

Gnomad4 AFR exome AF: 0.693

Gnomad4 AMR exome AF: 0.342

Gnomad4 ASJ exome AF: 0.424

Gnomad4 EAS exome AF: 0.483

Gnomad4 SAS exome AF: 0.286

Gnomad4 FIN exome AF: 0.449

Gnomad4 NFE exome AF: 0.438

Gnomad4 OTH exome AF: 0.443

GnomAD4 genome AF: 0.501 AC: 76112 AN: 151946 Hom.: 20282 Cov.: 0 AF XY: 0.496 AC XY: 36811 AN XY: 74248

Gnomad4 AFR AF: 0.688

Gnomad4 AMR AF: 0.413

Gnomad4 ASJ AF: 0.420

Gnomad4 EAS AF: 0.495

Gnomad4 SAS AF: 0.291

Gnomad4 FIN AF: 0.456

Gnomad4 NFE AF: 0.436

Gnomad4 OTH AF: 0.465

Alfa AF: 0.355 Hom.: 1486

Bravo AF: 0.507

Asia WGS AF: 0.397 AC: 1381 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 28, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

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 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: rs11291395; hg19: chr6-38885010; COSMIC: COSV59441523;