rs10496313

Variant names:

• chr2-84534631-A-G
• rs10496313
• NM_001370.2:c.662+5465A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001370.2(DNAH6):​c.662+5465A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0236 in 152,018 control chromosomes in the GnomAD database, including 57 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 0.024 (57 hom., cov: 32)
• Consequence: DNAH6 NM_001370.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0610

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.053 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH6	NM_001370.2	c.662+5465A>G		intron_variant	Intron 4 of 76	ENST00000389394.8	NP_001361.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH6	ENST00000389394.8	c.662+5465A>G		intron_variant	Intron 4 of 76	5	NM_001370.2	ENSP00000374045.3
DNAH6	ENST00000494025.1	n.230-13657A>G		intron_variant	Intron 1 of 8	1
DNAH6	ENST00000468661.1	n.454+8893A>G		intron_variant	Intron 3 of 3	4
DNAH6	ENST00000476689.5	n.536+8893A>G		intron_variant	Intron 3 of 10	2

Frequencies

GnomAD3 genomes AF: 0.0236 AC: 3580 AN: 151900 Hom.: 57 Cov.: 32

Gnomad AFR AF: 0.0395

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0280

Gnomad ASJ AF: 0.0473

Gnomad EAS AF: 0.0114

Gnomad SAS AF: 0.0586

Gnomad FIN AF: 0.00388

Gnomad MID AF: 0.0860

Gnomad NFE AF: 0.0127

Gnomad OTH AF: 0.0330

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

GnomAD4 genome AF: 0.0236 AC: 3588 AN: 152018 Hom.: 57 Cov.: 32 AF XY: 0.0238 AC XY: 1770 AN XY: 74312

Gnomad4 AFR AF: 0.0395 AC: 0.0394959 AN: 0.0394959

Gnomad4 AMR AF: 0.0280 AC: 0.0279785 AN: 0.0279785

Gnomad4 ASJ AF: 0.0473 AC: 0.0472895 AN: 0.0472895

Gnomad4 EAS AF: 0.0114 AC: 0.0113988 AN: 0.0113988

Gnomad4 SAS AF: 0.0586 AC: 0.0586035 AN: 0.0586035

Gnomad4 FIN AF: 0.00388 AC: 0.0038789 AN: 0.0038789

Gnomad4 NFE AF: 0.0127 AC: 0.0127439 AN: 0.0127439

Gnomad4 OTH AF: 0.0341 AC: 0.0341232 AN: 0.0341232

Alfa AF: 0.0193 Hom.: 13

Bravo AF: 0.0249

Asia WGS AF: 0.0400 AC: 139 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.7
DANN	Benign	0.76
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

Publications

LitVar

Other links and lift over

dbSNP: rs10496313; hg19: chr2-84761755;