rs1192372

Positions:

• chr2-84784422-T-C

Variant summary

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

The NM_001370.2(DNAH6):​c.10865-300T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 152,140 control chromosomes in the GnomAD database, including 4,095 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 0.22 (4095 hom., cov: 32)
• Consequence: DNAH6 NM_001370.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.356 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH6	NM_001370.2	c.10865-300T>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.10865-300T>C		intron_variant		5	NM_001370.2	ENSP00000374045.3

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32712 AN: 152022 Hom.: 4071 Cov.: 32

Gnomad AFR AF: 0.361

Gnomad AMI AF: 0.343

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.107

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.219

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

GnomAD4 genome AF: 0.215 AC: 32778 AN: 152140 Hom.: 4095 Cov.: 32 AF XY: 0.212 AC XY: 15806 AN XY: 74386

Gnomad4 AFR AF: 0.361

Gnomad4 AMR AF: 0.184

Gnomad4 ASJ AF: 0.176

Gnomad4 EAS AF: 0.106

Gnomad4 SAS AF: 0.139

Gnomad4 FIN AF: 0.157

Gnomad4 NFE AF: 0.157

Gnomad4 OTH AF: 0.219

Alfa AF: 0.171 Hom.: 1176

Bravo AF: 0.225

Asia WGS AF: 0.154 AC: 536 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.98
DANN	Benign	0.88

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: rs1192372; hg19: chr2-85011546;