rs10496314

Variant names:

• chr2-84580261-T-C
• rs10496314
• NM_001370.2:c.2229+582T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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]

DNAH6 Gene-Disease associations (from GenCC):

• male infertility with azoospermia or oligozoospermia due to single gene mutation

  Inheritance: AR Classification: MODERATE Submitted by: King Faisal Specialist Hospital and Research Center

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
DNAH6	NM_001370.2	c.2229+582T>C		intron_variant	Intron 14 of 76	ENST00000389394.8	NP_001361.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH6	ENST00000389394.8	c.2229+582T>C		intron_variant	Intron 14 of 76	5	NM_001370.2	ENSP00000374045.3
DNAH6	ENST00000494025.1	n.1272+582T>C		intron_variant	Intron 8 of 8	1
DNAH6	ENST00000476689.5	n.1579+582T>C		intron_variant	Intron 10 of 10	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

African (AFR) AF: 0.0208 AC: 863 AN: 41412

American (AMR) AF: 0.0385 AC: 587 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.0475 AC: 165 AN: 3472

East Asian (EAS) AF: 0.0112 AC: 58 AN: 5168

South Asian (SAS) AF: 0.0601 AC: 289 AN: 4812

European-Finnish (FIN) AF: 0.0102 AC: 108 AN: 10570

Middle Eastern (MID) AF: 0.103 AC: 30 AN: 292

European-Non Finnish (NFE) AF: 0.0235 AC: 1595 AN: 67946

Other (OTH) AF: 0.0412 AC: 87 AN: 2110

Alfa AF: 0.0246 Hom.: 18

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
PhyloP100		0.076
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs10496314; hg19: chr2-84807385;