2-84525506-A-C

Position:

• chr2-84525506-A-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001370.2(DNAH6):​c.226-59A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0302 in 1,486,364 control chromosomes in the GnomAD database, including 3,176 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.092 (1615 hom., cov: 32)
  • Exomes 𝑓: 0.023 (1561 hom.)
• Consequence: DNAH6 NM_001370.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.979

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 2-84525506-A-C is Benign according to our data. Variant chr2-84525506-A-C is described in ClinVar as [Benign]. Clinvar id is 1265934.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.272 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH6	NM_001370.2	c.226-59A>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.226-59A>C		intron_variant		5	NM_001370.2	ENSP00000374045.3
DNAH6	ENST00000494025.1	n.229+7455A>C		intron_variant		1
DNAH6	ENST00000468661.1	n.281-59A>C		intron_variant		4
DNAH6	ENST00000476689.5	n.363-59A>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0919 AC: 13971 AN: 152000 Hom.: 1613 Cov.: 32

Gnomad AFR AF: 0.277

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0535

Gnomad ASJ AF: 0.0479

Gnomad EAS AF: 0.0112

Gnomad SAS AF: 0.0595

Gnomad FIN AF: 0.00396

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0139

Gnomad OTH AF: 0.0809

GnomAD4 exome AF: 0.0231 AC: 30840 AN: 1334246 Hom.: 1561 AF XY: 0.0240 AC XY: 15810 AN XY: 659822

Gnomad4 AFR exome AF: 0.282

Gnomad4 AMR exome AF: 0.0370

Gnomad4 ASJ exome AF: 0.0514

Gnomad4 EAS exome AF: 0.0209

Gnomad4 SAS exome AF: 0.0610

Gnomad4 FIN exome AF: 0.00498

Gnomad4 NFE exome AF: 0.0122

Gnomad4 OTH exome AF: 0.0401

GnomAD4 genome AF: 0.0920 AC: 13992 AN: 152118 Hom.: 1615 Cov.: 32 AF XY: 0.0891 AC XY: 6627 AN XY: 74374

Gnomad4 AFR AF: 0.276

Gnomad4 AMR AF: 0.0534

Gnomad4 ASJ AF: 0.0479

Gnomad4 EAS AF: 0.0112

Gnomad4 SAS AF: 0.0592

Gnomad4 FIN AF: 0.00396

Gnomad4 NFE AF: 0.0139

Gnomad4 OTH AF: 0.0814

Alfa AF: 0.0595 Hom.: 113

Bravo AF: 0.102

Asia WGS AF: 0.0550 AC: 191 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 11, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	13
DANN	Benign	0.63

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: rs9784108; hg19: chr2-84752630;