NM_001206927.2:c.3034+9T>C

Variant names:

• chr6-38803320-T-C
• rs12192604
• NM_001206927.2:c.3034+9T>C

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.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
• Publications: 7 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 Gene-Disease associations (from GenCC):

• spermatogenic failure 46

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen
• spermatogenic failure 5

  Inheritance: AR Classification: MODERATE Submitted by: Franklin by Genoox
• primary ciliary dyskinesia

  Inheritance: AR Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH8	NM_001206927.2	MANE Select	c.3034+9T>C		intron	N/A	NP_001193856.1
	DNAH8	NM_001371.4		c.2383+9T>C		intron	N/A	NP_001362.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH8	ENST00000327475.11	TSL:5 MANE Select	c.3034+9T>C		intron	N/A	ENSP00000333363.7
	DNAH8	ENST00000359357.7	TSL:2	c.2383+9T>C		intron	N/A	ENSP00000352312.3
	DNAH8	ENST00000449981.6	TSL:5	c.3034+9T>C		intron	N/A	ENSP00000415331.2

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

GnomAD2 exomes AF: 0.151 AC: 36020 AN: 238588 AF XY: 0.157

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 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

African (AFR) AF: 0.0290 AC: 954 AN: 32842

American (AMR) AF: 0.0992 AC: 4182 AN: 42174

Ashkenazi Jewish (ASJ) AF: 0.223 AC: 5712 AN: 25630

East Asian (EAS) AF: 0.00318 AC: 125 AN: 39270

South Asian (SAS) AF: 0.133 AC: 10963 AN: 82208

European-Finnish (FIN) AF: 0.200 AC: 10656 AN: 53162

Middle Eastern (MID) AF: 0.194 AC: 1109 AN: 5706

European-Non Finnish (NFE) AF: 0.197 AC: 216241 AN: 1099928

Other (OTH) AF: 0.178 AC: 10628 AN: 59708

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

African (AFR) AF: 0.0348 AC: 1447 AN: 41566

American (AMR) AF: 0.133 AC: 2029 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.229 AC: 792 AN: 3466

East Asian (EAS) AF: 0.00347 AC: 18 AN: 5188

South Asian (SAS) AF: 0.122 AC: 588 AN: 4824

European-Finnish (FIN) AF: 0.200 AC: 2124 AN: 10608

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.197 AC: 13413 AN: 67974

Other (OTH) AF: 0.141 AC: 297 AN: 2112

Alfa AF: 0.168 Hom.: 1927

Bravo AF: 0.125

Asia WGS AF: 0.0680 AC: 235 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	-0.87
CADD	Benign	0.18
DANN	Benign	0.29
PhyloP100		-0.48
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: rs12192604; hg19: chr6-38771096; COSMIC: COSV59435222;