2-84482091-G-T

Position:

• chr2-84482091-G-T

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
DNAH6	XM_011532649.3	c.-9+22421G>T		intron_variant			XP_011530951.1
DNAH6	XM_011532650.4	c.-9+22416G>T		intron_variant			XP_011530952.1
		n.84482091G>T		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	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

Gnomad4 AFR AF: 0.135

Gnomad4 AMR AF: 0.303

Gnomad4 ASJ AF: 0.292

Gnomad4 EAS AF: 0.211

Gnomad4 SAS AF: 0.432

Gnomad4 FIN AF: 0.358

Gnomad4 NFE AF: 0.406

Gnomad4 OTH AF: 0.294

Alfa AF: 0.351 Hom.: 4349

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7581224; hg19: chr2-84709215;