rs7570005

Variant names:

• chr2-84634599-C-T
• rs7570005
• NM_001370.2:c.4611C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001370.2(DNAH6):​c.4611C>T​(p.Ile1537Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0952 in 1,548,974 control chromosomes in the GnomAD database, including 12,238 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.18 (4512 hom., cov: 32)
  • Exomes 𝑓: 0.086 (7726 hom.)
• Consequence: DNAH6 NM_001370.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -3.92
• Publications: 8 publications found

Genes affected

DNAH6 (HGNC:2951): (dynein axonemal heavy chain 6) This gene belongs to the dynein family, whose members encode large proteins that are constituents of the microtubule-associated motor protein complex. This complex is composed of dynein heavy, intermediate and light chains, which can be axonemal or cytoplasmic. This protein is an axonemal dynein heavy chain. It is involved in producing force for ciliary beating by using energy from ATP hydrolysis. Mutations in this gene may cause primary ciliary dyskinesia (PCD) as well as heterotaxy. [provided by RefSeq, Jun 2016]

DNAH6 Gene-Disease associations (from GenCC):

• male infertility with azoospermia or oligozoospermia due to single gene mutation

  Inheritance: AR Classification: MODERATE Submitted by: King Faisal Specialist Hospital and Research Center

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 2-84634599-C-T is Benign according to our data. Variant chr2-84634599-C-T is described in ClinVar as Benign. ClinVar VariationId is 402737.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.92 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.432 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001370.2. 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
	DNAH6	NM_001370.2	MANE Select	c.4611C>T	p.Ile1537Ile	synonymous	Exon 30 of 77	NP_001361.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH6	ENST00000389394.8	TSL:5 MANE Select	c.4611C>T	p.Ile1537Ile	synonymous	Exon 30 of 77	ENSP00000374045.3

Frequencies

GnomAD3 genomes AF: 0.178 AC: 27021 AN: 152094 Hom.: 4496 Cov.: 32

Gnomad AFR AF: 0.437

Gnomad AMI AF: 0.100

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.0605

Gnomad EAS AF: 0.0133

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.0508

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.0778

Gnomad OTH AF: 0.157

GnomAD2 exomes AF: 0.0899 AC: 13865 AN: 154154 AF XY: 0.0873

Gnomad AFR exome AF: 0.440

Gnomad AMR exome AF: 0.0688

Gnomad ASJ exome AF: 0.0622

Gnomad EAS exome AF: 0.00945

Gnomad FIN exome AF: 0.0474

Gnomad NFE exome AF: 0.0770

Gnomad OTH exome AF: 0.0855

GnomAD4 exome AF: 0.0861 AC: 120316 AN: 1396762 Hom.: 7726 Cov.: 30 AF XY: 0.0861 AC XY: 59299 AN XY: 688872

African (AFR) AF: 0.444 AC: 13894 AN: 31270

American (AMR) AF: 0.0751 AC: 2657 AN: 35358

Ashkenazi Jewish (ASJ) AF: 0.0621 AC: 1560 AN: 25116

East Asian (EAS) AF: 0.0219 AC: 780 AN: 35550

South Asian (SAS) AF: 0.109 AC: 8595 AN: 78746

European-Finnish (FIN) AF: 0.0467 AC: 2301 AN: 49262

Middle Eastern (MID) AF: 0.136 AC: 772 AN: 5686

European-Non Finnish (NFE) AF: 0.0777 AC: 83699 AN: 1077862

Other (OTH) AF: 0.105 AC: 6058 AN: 57912

GnomAD4 genome AF: 0.178 AC: 27083 AN: 152212 Hom.: 4512 Cov.: 32 AF XY: 0.174 AC XY: 12961 AN XY: 74432

African (AFR) AF: 0.437 AC: 18145 AN: 41506

American (AMR) AF: 0.119 AC: 1818 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0605 AC: 210 AN: 3472

East Asian (EAS) AF: 0.0133 AC: 69 AN: 5184

South Asian (SAS) AF: 0.110 AC: 532 AN: 4824

European-Finnish (FIN) AF: 0.0508 AC: 539 AN: 10604

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

European-Non Finnish (NFE) AF: 0.0778 AC: 5294 AN: 68016

Other (OTH) AF: 0.157 AC: 332 AN: 2116

Alfa AF: 0.122 Hom.: 1494

Bravo AF: 0.192

Asia WGS AF: 0.0890 AC: 309 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	DNAH6-related disorder (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	1.2
DANN	Benign	0.69
PhyloP100		-3.9
Mutation Taster		=99/1	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: rs7570005; hg19: chr2-84861723;