rs862432

Variant names:

• chr6-38883033-C-A
• rs862432
• NM_001206927.2:c.7982C>A

Your query was ambiguous. Multiple possible variants found:

• chr6-38883033-C-A
• chr6-38883033-C-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.7982C>A​(p.Thr2661Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0142 in 1,596,264 control chromosomes in the GnomAD database, including 1,974 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.065 (999 hom., cov: 33)
  • Exomes 𝑓: 0.0089 (975 hom.)
• Consequence: DNAH8 NM_001206927.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 4.92
• Publications: 9 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 (MetaRNN=0.001779288).
• BP6: Variant 6-38883033-C-A is Benign according to our data. Variant chr6-38883033-C-A is described in ClinVar as Benign. ClinVar VariationId is 414377.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.212 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH8	NM_001206927.2	MANE Select	c.7982C>A	p.Thr2661Asn	missense	Exon 54 of 93	NP_001193856.1
	DNAH8	NM_001371.4		c.7331C>A	p.Thr2444Asn	missense	Exon 53 of 92	NP_001362.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH8	ENST00000327475.11	TSL:5 MANE Select	c.7982C>A	p.Thr2661Asn	missense	Exon 54 of 93	ENSP00000333363.7
	DNAH8	ENST00000359357.7	TSL:2	c.7331C>A	p.Thr2444Asn	missense	Exon 52 of 91	ENSP00000352312.3
	DNAH8	ENST00000449981.6	TSL:5	c.7982C>A	p.Thr2661Asn	missense	Exon 53 of 82	ENSP00000415331.2

Frequencies

GnomAD3 genomes AF: 0.0650 AC: 9876 AN: 152012 Hom.: 995 Cov.: 33

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0328

Gnomad ASJ AF: 0.0288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00187

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.00309

Gnomad OTH AF: 0.0527

GnomAD2 exomes AF: 0.0200 AC: 4732 AN: 236978 AF XY: 0.0154

Gnomad AFR exome AF: 0.225

Gnomad AMR exome AF: 0.0163

Gnomad ASJ exome AF: 0.0285

Gnomad EAS exome AF: 0.0000571

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00273

Gnomad OTH exome AF: 0.0118

GnomAD4 exome AF: 0.00885 AC: 12787 AN: 1444134 Hom.: 975 Cov.: 30 AF XY: 0.00805 AC XY: 5780 AN XY: 717874

African (AFR) AF: 0.230 AC: 7457 AN: 32428

American (AMR) AF: 0.0189 AC: 770 AN: 40780

Ashkenazi Jewish (ASJ) AF: 0.0279 AC: 717 AN: 25680

East Asian (EAS) AF: 0.0000255 AC: 1 AN: 39144

South Asian (SAS) AF: 0.00242 AC: 197 AN: 81392

European-Finnish (FIN) AF: 0.0000376 AC: 2 AN: 53190

Middle Eastern (MID) AF: 0.0348 AC: 198 AN: 5694

European-Non Finnish (NFE) AF: 0.00213 AC: 2361 AN: 1106174

Other (OTH) AF: 0.0182 AC: 1084 AN: 59652

GnomAD4 genome AF: 0.0651 AC: 9904 AN: 152130 Hom.: 999 Cov.: 33 AF XY: 0.0633 AC XY: 4708 AN XY: 74360

African (AFR) AF: 0.216 AC: 8963 AN: 41460

American (AMR) AF: 0.0328 AC: 501 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0288 AC: 100 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00187 AC: 9 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10590

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.00309 AC: 210 AN: 68008

Other (OTH) AF: 0.0521 AC: 110 AN: 2110

Alfa AF: 0.0267 Hom.: 1198

Bravo AF: 0.0760

TwinsUK AF: 0.00324 AC: 12

ALSPAC AF: 0.00182 AC: 7

ESP6500AA AF: 0.208 AC: 915

ESP6500EA AF: 0.00338 AC: 29

ExAC AF: 0.0233 AC: 2825

Asia WGS AF: 0.0140 AC: 49 AN: 3470

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.081	T
Eigen	Pathogenic	0.73
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.89	D
MetaRNN	Benign	0.0018	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		4.9
PrimateAI	Uncertain	0.64	T
PROVEAN	Pathogenic	-4.5	D
REVEL	Uncertain	0.32
Sift	Benign	0.13	T
Polyphen		1.0	D
Vest4		0.61
MPC		0.60
ClinPred		0.022	T
GERP RS		5.9
Varity_R		0.63
gMVP		0.83
Mutation Taster		=94/6	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: rs862432; hg19: chr6-38850809; COSMIC: COSV59473057;