rs10496314

Positions:

• chr2-84580261-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.2229+582T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.025 in 151,946 control chromosomes in the GnomAD database, including 56 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 0.025 (56 hom., cov: 32)
• Consequence: DNAH6 NM_001370.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0760

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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0544 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH6	NM_001370.2	c.2229+582T>C		intron_variant		ENST00000389394.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH6	ENST00000389394.8	c.2229+582T>C		intron_variant		5	NM_001370.2	P1
DNAH6	ENST00000494025.1	n.1272+582T>C		intron_variant, non_coding_transcript_variant		1
DNAH6	ENST00000476689.5	n.1579+582T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0249 AC: 3788 AN: 151828 Hom.: 56 Cov.: 32

Gnomad AFR AF: 0.0208

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0385

Gnomad ASJ AF: 0.0475

Gnomad EAS AF: 0.0112

Gnomad SAS AF: 0.0598

Gnomad FIN AF: 0.0102

Gnomad MID AF: 0.105

Gnomad NFE AF: 0.0235

Gnomad OTH AF: 0.0402

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

GnomAD4 genome AF: 0.0250 AC: 3795 AN: 151946 Hom.: 56 Cov.: 32 AF XY: 0.0253 AC XY: 1879 AN XY: 74276

Gnomad4 AFR AF: 0.0208

Gnomad4 AMR AF: 0.0385

Gnomad4 ASJ AF: 0.0475

Gnomad4 EAS AF: 0.0112

Gnomad4 SAS AF: 0.0601

Gnomad4 FIN AF: 0.0102

Gnomad4 NFE AF: 0.0235

Gnomad4 OTH AF: 0.0412

Alfa AF: 0.0234 Hom.: 9

Bravo AF: 0.0258

Asia WGS AF: 0.0390 AC: 135 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.7
DANN	Benign	0.67

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: rs10496314; hg19: chr2-84807385;