rs10947765

Variant names:

• chr6-38951533-A-G
• rs10947765
• NM_001206927.2:c.12451+13A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001206927.2(DNAH8):​c.12451+13A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 1,602,042 control chromosomes in the GnomAD database, including 12,335 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (1590 hom., cov: 32)
  • Exomes 𝑓: 0.12 (10745 hom.)
• Consequence: DNAH8 NM_001206927.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.00500
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 6-38951533-A-G is Benign according to our data. Variant chr6-38951533-A-G is described in ClinVar as Benign. ClinVar VariationId is 402769.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.212 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.12451+13A>G		intron	N/A	NP_001193856.1
	DNAH8	NM_001371.4		c.11800+13A>G		intron	N/A	NP_001362.2
	DNAH8-AS1	NR_038401.1		n.60+1515T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH8	ENST00000327475.11	TSL:5 MANE Select	c.12451+13A>G		intron	N/A	ENSP00000333363.7
	DNAH8	ENST00000359357.7	TSL:2	c.11800+13A>G		intron	N/A	ENSP00000352312.3
	DNAH8	ENST00000449981.6	TSL:5	c.12451+13A>G		intron	N/A	ENSP00000415331.2

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21326 AN: 152106 Hom.: 1580 Cov.: 32

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.0570

Gnomad AMR AF: 0.218

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.164

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.136

GnomAD2 exomes AF: 0.146 AC: 35669 AN: 244906 AF XY: 0.141

Gnomad AFR exome AF: 0.168

Gnomad AMR exome AF: 0.270

Gnomad ASJ exome AF: 0.135

Gnomad EAS exome AF: 0.158

Gnomad FIN exome AF: 0.109

Gnomad NFE exome AF: 0.113

Gnomad OTH exome AF: 0.137

GnomAD4 exome AF: 0.118 AC: 170439 AN: 1449818 Hom.: 10745 Cov.: 30 AF XY: 0.117 AC XY: 84513 AN XY: 719360

African (AFR) AF: 0.177 AC: 5883 AN: 33154

American (AMR) AF: 0.256 AC: 11202 AN: 43822

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 3609 AN: 25844

East Asian (EAS) AF: 0.150 AC: 5928 AN: 39518

South Asian (SAS) AF: 0.135 AC: 11350 AN: 84310

European-Finnish (FIN) AF: 0.108 AC: 5785 AN: 53324

Middle Eastern (MID) AF: 0.112 AC: 639 AN: 5728

European-Non Finnish (NFE) AF: 0.108 AC: 118905 AN: 1104158

Other (OTH) AF: 0.119 AC: 7138 AN: 59960

GnomAD4 genome AF: 0.140 AC: 21364 AN: 152224 Hom.: 1590 Cov.: 32 AF XY: 0.143 AC XY: 10621 AN XY: 74416

African (AFR) AF: 0.168 AC: 6974 AN: 41522

American (AMR) AF: 0.218 AC: 3337 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 439 AN: 3466

East Asian (EAS) AF: 0.165 AC: 853 AN: 5178

South Asian (SAS) AF: 0.138 AC: 662 AN: 4812

European-Finnish (FIN) AF: 0.108 AC: 1142 AN: 10614

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.111 AC: 7575 AN: 68020

Other (OTH) AF: 0.138 AC: 291 AN: 2112

Alfa AF: 0.123 Hom.: 339

Bravo AF: 0.149

Asia WGS AF: 0.173 AC: 601 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.7
DANN	Benign	0.43
PhyloP100		-0.0050
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
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

Other links and lift over

dbSNP: rs10947765; hg19: chr6-38919309; COSMIC: COSV107384219;