rs1037863

Variant names:

• chr2-84544356-G-A
• rs1037863
• NM_001370.2:c.786G>A

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.786G>A​(p.Leu262Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.944 in 1,544,810 control chromosomes in the GnomAD database, including 689,075 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.92 (64732 hom., cov: 31)
  • Exomes 𝑓: 0.95 (624343 hom.)
• Consequence: DNAH6 NM_001370.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -3.61
• Publications: 13 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):

• spermatogenic failure

  Inheritance: AR Classification: STRONG Submitted by: ClinGen
• male infertility with azoospermia or oligozoospermia due to single gene mutation

  Inheritance: AR Classification: MODERATE Submitted by: King Faisal Specialist Hospital and Research Center
• primary ciliary dyskinesia

  Inheritance: AR Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 2-84544356-G-A is Benign according to our data. Variant chr2-84544356-G-A is described in ClinVar as Benign. ClinVar VariationId is 402732.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.61 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH6	NM_001370.2	MANE Select	c.786G>A	p.Leu262Leu	synonymous	Exon 5 of 77	NP_001361.1	Q9C0G6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH6	ENST00000389394.8	TSL:5 MANE Select	c.786G>A	p.Leu262Leu	synonymous	Exon 5 of 77	ENSP00000374045.3	Q9C0G6-1
	DNAH6	ENST00000494025.1	TSL:1	n.230-3932G>A		intron	N/A
	DNAH6	ENST00000476689.5	TSL:2	n.537-3932G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.921 AC: 140005 AN: 151998 Hom.: 64701 Cov.: 31

Gnomad AFR AF: 0.840

Gnomad AMI AF: 0.916

Gnomad AMR AF: 0.950

Gnomad ASJ AF: 0.984

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.950

Gnomad FIN AF: 0.959

Gnomad MID AF: 0.949

Gnomad NFE AF: 0.947

Gnomad OTH AF: 0.936

GnomAD2 exomes AF: 0.953 AC: 148898 AN: 156226 AF XY: 0.955

Gnomad AFR exome AF: 0.834

Gnomad AMR exome AF: 0.970

Gnomad ASJ exome AF: 0.985

Gnomad EAS exome AF: 0.999

Gnomad FIN exome AF: 0.962

Gnomad NFE exome AF: 0.947

Gnomad OTH exome AF: 0.958

GnomAD4 exome AF: 0.947 AC: 1318246 AN: 1392694 Hom.: 624343 Cov.: 38 AF XY: 0.947 AC XY: 651145 AN XY: 687366

African (AFR) AF: 0.832 AC: 26172 AN: 31460

American (AMR) AF: 0.969 AC: 34566 AN: 35686

Ashkenazi Jewish (ASJ) AF: 0.985 AC: 24729 AN: 25100

East Asian (EAS) AF: 0.999 AC: 35555 AN: 35588

South Asian (SAS) AF: 0.952 AC: 75320 AN: 79080

European-Finnish (FIN) AF: 0.962 AC: 47381 AN: 49260

Middle Eastern (MID) AF: 0.954 AC: 5420 AN: 5684

European-Non Finnish (NFE) AF: 0.945 AC: 1014560 AN: 1073086

Other (OTH) AF: 0.944 AC: 54543 AN: 57750

GnomAD4 genome AF: 0.921 AC: 140092 AN: 152116 Hom.: 64732 Cov.: 31 AF XY: 0.923 AC XY: 68617 AN XY: 74360

African (AFR) AF: 0.839 AC: 34803 AN: 41470

American (AMR) AF: 0.951 AC: 14522 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.984 AC: 3416 AN: 3472

East Asian (EAS) AF: 0.997 AC: 5168 AN: 5182

South Asian (SAS) AF: 0.950 AC: 4584 AN: 4826

European-Finnish (FIN) AF: 0.959 AC: 10167 AN: 10600

Middle Eastern (MID) AF: 0.946 AC: 278 AN: 294

European-Non Finnish (NFE) AF: 0.947 AC: 64342 AN: 67972

Other (OTH) AF: 0.937 AC: 1977 AN: 2110

Alfa AF: 0.938 Hom.: 35824

Bravo AF: 0.918

Asia WGS AF: 0.966 AC: 3350 AN: 3468

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.13
DANN	Benign	0.59
PhyloP100		-3.6
Mutation Taster		=86/14	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: rs1037863; hg19: chr2-84771480; COSMIC: COSV108041473; COSMIC: COSV108041473;