rs10947765

chr6-38951533-A-G

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.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

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

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH8	NM_001206927.2	c.12451+13A>G		intron_variant		ENST00000327475.11
DNAH8-AS1	NR_038401.1	n.60+1515T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH8	ENST00000327475.11	c.12451+13A>G		intron_variant		5	NM_001206927.2	P2
DNAH8-AS1	ENST00000416948.1	n.52+1515T>C		intron_variant, non_coding_transcript_variant		2
DNAH8	ENST00000359357.7	c.11800+13A>G		intron_variant		2		A2
DNAH8	ENST00000449981.6	c.12451+13A>G		intron_variant		5

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

GnomAD3 exomes AF: 0.146 AC: 35669 AN: 244906 Hom.: 2967 AF XY: 0.141 AC XY: 18619 AN XY: 131946

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 SAS exome AF: 0.140

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

Gnomad4 AFR exome AF: 0.177

Gnomad4 AMR exome AF: 0.256

Gnomad4 ASJ exome AF: 0.140

Gnomad4 EAS exome AF: 0.150

Gnomad4 SAS exome AF: 0.135

Gnomad4 FIN exome AF: 0.108

Gnomad4 NFE exome AF: 0.108

Gnomad4 OTH exome AF: 0.119

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

Gnomad4 AFR AF: 0.168

Gnomad4 AMR AF: 0.218

Gnomad4 ASJ AF: 0.127

Gnomad4 EAS AF: 0.165

Gnomad4 SAS AF: 0.138

Gnomad4 FIN AF: 0.108

Gnomad4 NFE AF: 0.111

Gnomad4 OTH AF: 0.138

Alfa AF: 0.122 Hom.: 325

Bravo AF: 0.149

Asia WGS AF: 0.173 AC: 601 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

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

May 12, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	3.7
Dann	Benign	0.43

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

Publications

LitVar

Other links and lift over

dbSNP: rs10947765; hg19: chr6-38919309;