rs72832550

Variant names:

• chr2-84733470-C-G
• rs72832550
• NM_001370.2:c.10233C>G

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_001370.2(DNAH6):​c.10233C>G​(p.Pro3411Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00247 in 1,551,420 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0016 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0026 (10 hom.)
• Consequence: DNAH6 NM_001370.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.0110
• Publications: 2 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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BP6: Variant 2-84733470-C-G is Benign according to our data. Variant chr2-84733470-C-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 402747.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.011 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 10 AR gene

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.10233C>G	p.Pro3411Pro	synonymous	Exon 62 of 77	NP_001361.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH6	ENST00000389394.8	TSL:5 MANE Select	c.10233C>G	p.Pro3411Pro	synonymous	Exon 62 of 77	ENSP00000374045.3

Frequencies

GnomAD3 genomes AF: 0.00161 AC: 245 AN: 152210 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000555

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00190

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00259

Gnomad OTH AF: 0.00335

GnomAD2 exomes AF: 0.00168 AC: 263 AN: 156514 AF XY: 0.00181

Gnomad AFR exome AF: 0.000378

Gnomad AMR exome AF: 0.000811

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000918

Gnomad FIN exome AF: 0.000178

Gnomad NFE exome AF: 0.00292

Gnomad OTH exome AF: 0.000910

GnomAD4 exome AF: 0.00256 AC: 3588 AN: 1399092 Hom.: 10 Cov.: 30 AF XY: 0.00263 AC XY: 1815 AN XY: 690080

African (AFR) AF: 0.000443 AC: 14 AN: 31594

American (AMR) AF: 0.00109 AC: 39 AN: 35696

Ashkenazi Jewish (ASJ) AF: 0.0000795 AC: 2 AN: 25170

East Asian (EAS) AF: 0.0000280 AC: 1 AN: 35724

South Asian (SAS) AF: 0.00231 AC: 183 AN: 79198

European-Finnish (FIN) AF: 0.000122 AC: 6 AN: 49272

Middle Eastern (MID) AF: 0.000176 AC: 1 AN: 5698

European-Non Finnish (NFE) AF: 0.00296 AC: 3190 AN: 1078746

Other (OTH) AF: 0.00262 AC: 152 AN: 57994

GnomAD4 genome AF: 0.00161 AC: 245 AN: 152328 Hom.: 0 Cov.: 32 AF XY: 0.00153 AC XY: 114 AN XY: 74494

African (AFR) AF: 0.000553 AC: 23 AN: 41578

American (AMR) AF: 0.00189 AC: 29 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00207 AC: 10 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00259 AC: 176 AN: 68018

Other (OTH) AF: 0.00331 AC: 7 AN: 2114

Alfa AF: 0.00197 Hom.: 0

Bravo AF: 0.00167

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	DNAH6-related disorder (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	6.4
DANN	Benign	0.69
PhyloP100		0.011
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs72832550; hg19: chr2-84960594;