2-84482091-G-T

Variant names:

• chr2-84482091-G-T
• rs7581224
• XM_011532649.3:c.-9+22421G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_011532649.3(DNAH6):​c.-9+22421G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 151,938 control chromosomes in the GnomAD database, including 8,337 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.31 (8337 hom., cov: 32)
• Consequence: DNAH6 XM_011532649.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0980
• Publications: 18 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.416 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH6	XM_011532649.3	c.-9+22421G>T		intron_variant	Intron 1 of 76		XP_011530951.1
DNAH6	XM_011532650.4	c.-9+22416G>T		intron_variant	Intron 1 of 76		XP_011530952.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.308 AC: 46785 AN: 151820 Hom.: 8341 Cov.: 32

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.387

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.292

Gnomad EAS AF: 0.212

Gnomad SAS AF: 0.432

Gnomad FIN AF: 0.358

Gnomad MID AF: 0.299

Gnomad NFE AF: 0.406

Gnomad OTH AF: 0.297

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.308 AC: 46784 AN: 151938 Hom.: 8337 Cov.: 32 AF XY: 0.307 AC XY: 22766 AN XY: 74256

African (AFR) AF: 0.135 AC: 5603 AN: 41466

American (AMR) AF: 0.303 AC: 4622 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.292 AC: 1014 AN: 3468

East Asian (EAS) AF: 0.211 AC: 1087 AN: 5160

South Asian (SAS) AF: 0.432 AC: 2081 AN: 4820

European-Finnish (FIN) AF: 0.358 AC: 3773 AN: 10544

Middle Eastern (MID) AF: 0.295 AC: 86 AN: 292

European-Non Finnish (NFE) AF: 0.406 AC: 27545 AN: 67914

Other (OTH) AF: 0.294 AC: 621 AN: 2110

Alfa AF: 0.347 Hom.: 6485

Bravo AF: 0.287

Asia WGS AF: 0.289 AC: 1003 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.1
DANN	Benign	0.79
PhyloP100		-0.098

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7581224; hg19: chr2-84709215;