rs1192368

Positions:

• chr2-84806215-A-C
• chr2-84806215-A-G
• chr2-84806215-A-T

Variant summary

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

The NM_001370.2(DNAH6):​c.11611+421A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 152,160 control chromosomes in the GnomAD database, including 5,615 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 0.25 (5615 hom., cov: 32)
• Consequence: DNAH6 NM_001370.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.581

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.414 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH6	NM_001370.2	c.11611+421A>C		intron_variant		ENST00000389394.8	NP_001361.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH6	ENST00000389394.8	c.11611+421A>C		intron_variant		5	NM_001370.2	ENSP00000374045	P1

Frequencies

GnomAD3 genomes AF: 0.254 AC: 38654 AN: 152042 Hom.: 5592 Cov.: 32

Gnomad AFR AF: 0.418

Gnomad AMI AF: 0.346

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.108

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.194

Gnomad OTH AF: 0.251

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

GnomAD4 genome AF: 0.255 AC: 38727 AN: 152160 Hom.: 5615 Cov.: 32 AF XY: 0.251 AC XY: 18684 AN XY: 74390

Gnomad4 AFR AF: 0.419

Gnomad4 AMR AF: 0.212

Gnomad4 ASJ AF: 0.188

Gnomad4 EAS AF: 0.108

Gnomad4 SAS AF: 0.199

Gnomad4 FIN AF: 0.175

Gnomad4 NFE AF: 0.194

Gnomad4 OTH AF: 0.250

Alfa AF: 0.138 Hom.: 335

Bravo AF: 0.264

Asia WGS AF: 0.185 AC: 643 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.44
DANN	Benign	0.43

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: rs1192368; hg19: chr2-85033339;