rs11291395

Variant names:

• chr6-38917234-TA-T
• rs11291395
• NM_001206927.2:c.10141-4delA

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001206927.2(DNAH8):​c.10141-4delA variant causes a splice region, 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, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.492
• Publications: 5 publications found

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:40188): (DNAH8 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 257626.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.682 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001206927.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH8	NM_001206927.2	MANE Select	c.10141-4delA		splice_region intron	N/A	NP_001193856.1	A0A075B6F3
	DNAH8	NM_001371.4		c.9490-4delA		splice_region intron	N/A	NP_001362.2	Q96JB1-1
	DNAH8-AS1	NR_038401.1		n.782+5850delT		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH8	ENST00000327475.11	TSL:5 MANE Select	c.10141-4delA		splice_region intron	N/A	ENSP00000333363.7	A0A075B6F3
	DNAH8	ENST00000359357.7	TSL:2	c.9490-4delA		splice_region intron	N/A	ENSP00000352312.3	Q96JB1-1
	DNAH8	ENST00000449981.6	TSL:5	c.10141-4delA		splice_region intron	N/A	ENSP00000415331.2	H0Y7V4

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

GnomAD2 exomes AF: 0.427 AC: 104301 AN: 244146 AF XY: 0.418

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 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

African (AFR) AF: 0.693 AC: 22814 AN: 32902

American (AMR) AF: 0.342 AC: 14896 AN: 43530

Ashkenazi Jewish (ASJ) AF: 0.424 AC: 10903 AN: 25712

East Asian (EAS) AF: 0.483 AC: 19071 AN: 39520

South Asian (SAS) AF: 0.286 AC: 23917 AN: 83668

European-Finnish (FIN) AF: 0.449 AC: 23657 AN: 52712

Middle Eastern (MID) AF: 0.443 AC: 2520 AN: 5686

European-Non Finnish (NFE) AF: 0.438 AC: 483913 AN: 1103790

Other (OTH) AF: 0.443 AC: 26456 AN: 59782

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

African (AFR) AF: 0.688 AC: 28525 AN: 41448

American (AMR) AF: 0.413 AC: 6311 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.420 AC: 1454 AN: 3466

East Asian (EAS) AF: 0.495 AC: 2551 AN: 5156

South Asian (SAS) AF: 0.291 AC: 1401 AN: 4816

European-Finnish (FIN) AF: 0.456 AC: 4804 AN: 10534

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.436 AC: 29645 AN: 67936

Other (OTH) AF: 0.465 AC: 982 AN: 2112

Alfa AF: 0.355 Hom.: 1486

Bravo AF: 0.507

Asia WGS AF: 0.397 AC: 1381 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	1	not provided (1)
-	-	1	Primary ciliary dyskinesia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.49
Mutation Taster		=34/66	disease causing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs11291395;

hg19: chr6-38885010;

COSMIC: COSV59441523;