rs6729553

chr2-84682711-G-Achr2-84682711-G-Cchr2-84682711-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001370.2(DNAH6):c.6916+1183G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.748 in 152,078 control chromosomes in the GnomAD database, including 42,914 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 0.75 (42914 hom., cov: 31)
• Consequence: DNAH6 NM_001370.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.699

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.896 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH6	NM_001370.2	c.6916+1183G>A		intron_variant		ENST00000389394.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH6	ENST00000389394.8	c.6916+1183G>A		intron_variant		5	NM_001370.2	P1
DNAH6	ENST00000602588.1	n.1144+1183G>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.748 AC: 113594 AN: 151960 Hom.: 42885 Cov.: 31

Gnomad AFR AF: 0.628

Gnomad AMI AF: 0.588

Gnomad AMR AF: 0.799

Gnomad ASJ AF: 0.741

Gnomad EAS AF: 0.918

Gnomad SAS AF: 0.829

Gnomad FIN AF: 0.812

Gnomad MID AF: 0.777

Gnomad NFE AF: 0.782

Gnomad OTH AF: 0.753

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

GnomAD4 genome AF: 0.748 AC: 113685 AN: 152078 Hom.: 42914 Cov.: 31 AF XY: 0.752 AC XY: 55910 AN XY: 74338

Gnomad4 AFR AF: 0.628

Gnomad4 AMR AF: 0.799

Gnomad4 ASJ AF: 0.741

Gnomad4 EAS AF: 0.918

Gnomad4 SAS AF: 0.829

Gnomad4 FIN AF: 0.812

Gnomad4 NFE AF: 0.782

Gnomad4 OTH AF: 0.754

Alfa AF: 0.775 Hom.: 20640

Bravo AF: 0.742

Asia WGS AF: 0.844 AC: 2935 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	0.18
Dann	Benign	0.26

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

Publications

LitVar

Other links and lift over

dbSNP: rs6729553; hg19: chr2-84909835;