2-84525506-A-C

Variant names:

• chr2-84525506-A-C
• rs9784108
• NM_001370.2:c.226-59A>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001370.2(DNAH6):​c.226-59A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0302 in 1,486,364 control chromosomes in the GnomAD database, including 3,176 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.092 (1615 hom., cov: 32)
  • Exomes 𝑓: 0.023 (1561 hom.)
• Consequence: DNAH6 NM_001370.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.979
• Publications: 5 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 2-84525506-A-C is Benign according to our data. Variant chr2-84525506-A-C is described in ClinVar as Benign. ClinVar VariationId is 1265934.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.272 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.226-59A>C		intron	N/A	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.226-59A>C		intron	N/A	ENSP00000374045.3	Q9C0G6-1
	DNAH6	ENST00000494025.1	TSL:1	n.229+7455A>C		intron	N/A
	DNAH6	ENST00000468661.1	TSL:4	n.281-59A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0919 AC: 13971 AN: 152000 Hom.: 1613 Cov.: 32

Gnomad AFR AF: 0.277

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0535

Gnomad ASJ AF: 0.0479

Gnomad EAS AF: 0.0112

Gnomad SAS AF: 0.0595

Gnomad FIN AF: 0.00396

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0139

Gnomad OTH AF: 0.0809

GnomAD4 exome AF: 0.0231 AC: 30840 AN: 1334246 Hom.: 1561 AF XY: 0.0240 AC XY: 15810 AN XY: 659822

African (AFR) AF: 0.282 AC: 8020 AN: 28438

American (AMR) AF: 0.0370 AC: 910 AN: 24604

Ashkenazi Jewish (ASJ) AF: 0.0514 AC: 1208 AN: 23516

East Asian (EAS) AF: 0.0209 AC: 737 AN: 35260

South Asian (SAS) AF: 0.0610 AC: 4361 AN: 71448

European-Finnish (FIN) AF: 0.00498 AC: 243 AN: 48790

Middle Eastern (MID) AF: 0.0812 AC: 419 AN: 5160

European-Non Finnish (NFE) AF: 0.0122 AC: 12720 AN: 1041558

Other (OTH) AF: 0.0401 AC: 2222 AN: 55472

GnomAD4 genome AF: 0.0920 AC: 13992 AN: 152118 Hom.: 1615 Cov.: 32 AF XY: 0.0891 AC XY: 6627 AN XY: 74374

African (AFR) AF: 0.276 AC: 11464 AN: 41462

American (AMR) AF: 0.0534 AC: 815 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.0479 AC: 166 AN: 3468

East Asian (EAS) AF: 0.0112 AC: 58 AN: 5172

South Asian (SAS) AF: 0.0592 AC: 285 AN: 4818

European-Finnish (FIN) AF: 0.00396 AC: 42 AN: 10616

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.0139 AC: 945 AN: 68004

Other (OTH) AF: 0.0814 AC: 172 AN: 2112

Alfa AF: 0.0671 Hom.: 135

Bravo AF: 0.102

Asia WGS AF: 0.0550 AC: 191 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	13
DANN	Benign	0.63
PhyloP100		0.98
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: rs9784108; hg19: chr2-84752630;