rs12192604

Positions:

• chr6-38803320-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.3034+9T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 1,592,854 control chromosomes in the GnomAD database, including 27,357 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (1934 hom., cov: 32)
  • Exomes 𝑓: 0.18 (25423 hom.)
• Consequence: DNAH8 NM_001206927.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.482

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=-0.87).
• BP6: Variant 6-38803320-T-C is Benign according to our data. Variant chr6-38803320-T-C is described in ClinVar as [Benign]. Clinvar id is 257631.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.195 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH8	NM_001206927.2	c.3034+9T>C		intron_variant		ENST00000327475.11	NP_001193856.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH8	ENST00000327475.11	c.3034+9T>C		intron_variant		5	NM_001206927.2	ENSP00000333363	P2
DNAH8	ENST00000359357.7	c.2383+9T>C		intron_variant		2		ENSP00000352312	A2
DNAH8	ENST00000449981.6	c.3034+9T>C		intron_variant		5		ENSP00000415331

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20878 AN: 152108 Hom.: 1935 Cov.: 32

Gnomad AFR AF: 0.0349

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.229

Gnomad EAS AF: 0.00346

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.197

Gnomad OTH AF: 0.142

GnomAD3 exomes AF: 0.151 AC: 36020 AN: 238588 Hom.: 3337 AF XY: 0.157 AC XY: 20179 AN XY: 128822

Gnomad AFR exome AF: 0.0300

Gnomad AMR exome AF: 0.0959

Gnomad ASJ exome AF: 0.230

Gnomad EAS exome AF: 0.00372

Gnomad SAS exome AF: 0.133

Gnomad FIN exome AF: 0.198

Gnomad NFE exome AF: 0.194

Gnomad OTH exome AF: 0.183

GnomAD4 exome AF: 0.181 AC: 260570 AN: 1440628 Hom.: 25423 Cov.: 27 AF XY: 0.181 AC XY: 129635 AN XY: 716320

Gnomad4 AFR exome AF: 0.0290

Gnomad4 AMR exome AF: 0.0992

Gnomad4 ASJ exome AF: 0.223

Gnomad4 EAS exome AF: 0.00318

Gnomad4 SAS exome AF: 0.133

Gnomad4 FIN exome AF: 0.200

Gnomad4 NFE exome AF: 0.197

Gnomad4 OTH exome AF: 0.178

GnomAD4 genome AF: 0.137 AC: 20874 AN: 152226 Hom.: 1934 Cov.: 32 AF XY: 0.136 AC XY: 10133 AN XY: 74426

Gnomad4 AFR AF: 0.0348

Gnomad4 AMR AF: 0.133

Gnomad4 ASJ AF: 0.229

Gnomad4 EAS AF: 0.00347

Gnomad4 SAS AF: 0.122

Gnomad4 FIN AF: 0.200

Gnomad4 NFE AF: 0.197

Gnomad4 OTH AF: 0.141

Alfa AF: 0.174 Hom.: 1247

Bravo AF: 0.125

Asia WGS AF: 0.0680 AC: 235 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

Labcorp Genetics (formerly Invitae), Labcorp

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	-0.87
CADD	Benign	0.18
DANN	Benign	0.29

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: rs12192604; hg19: chr6-38771096; COSMIC: COSV59435222;