2-84528872-A-AT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001370.2(DNAH6):c.400-21dup variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.65 (32476 hom., cov: 0)
  • Exomes 𝑓: 0.49 (70136 hom.)
  • Failed GnomAD Quality Control
• Consequence: DNAH6 NM_001370.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.797

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 -10 ACMG points.

• BP6: Variant 2-84528872-A-AT is Benign according to our data. Variant chr2-84528872-A-AT is described in ClinVar as [Benign]. Clinvar id is 1281178.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.809 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH6	NM_001370.2	c.400-21dup		intron_variant		ENST00000389394.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH6	ENST00000389394.8	c.400-21dup		intron_variant		5	NM_001370.2	P1
DNAH6	ENST00000494025.1	n.229+10832dup		intron_variant, non_coding_transcript_variant		1
DNAH6	ENST00000468661.1	n.454+3145dup		intron_variant, non_coding_transcript_variant		4
DNAH6	ENST00000476689.5	n.536+3145dup		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.655 AC: 97148 AN: 148396 Hom.: 32464 Cov.: 0

Gnomad AFR AF: 0.757

Gnomad AMI AF: 0.493

Gnomad AMR AF: 0.671

Gnomad ASJ AF: 0.698

Gnomad EAS AF: 0.830

Gnomad SAS AF: 0.654

Gnomad FIN AF: 0.590

Gnomad MID AF: 0.705

Gnomad NFE AF: 0.585

Gnomad OTH AF: 0.678

GnomAD3 exomes AF: 0.508 AC: 46245 AN: 91098 Hom.: 5386 AF XY: 0.501 AC XY: 24176 AN XY: 48272

Gnomad AFR exome AF: 0.569

Gnomad AMR exome AF: 0.537

Gnomad ASJ exome AF: 0.514

Gnomad EAS exome AF: 0.580

Gnomad SAS exome AF: 0.484

Gnomad FIN exome AF: 0.506

Gnomad NFE exome AF: 0.487

Gnomad OTH exome AF: 0.514

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.491 AC: 569393 AN: 1159378 Hom.: 70136 Cov.: 33 AF XY: 0.490 AC XY: 278944 AN XY: 569402

Gnomad4 AFR exome AF: 0.567

Gnomad4 AMR exome AF: 0.534

Gnomad4 ASJ exome AF: 0.526

Gnomad4 EAS exome AF: 0.596

Gnomad4 SAS exome AF: 0.487

Gnomad4 FIN exome AF: 0.490

Gnomad4 NFE exome AF: 0.483

Gnomad4 OTH exome AF: 0.508

GnomAD4 genome AF: 0.655 AC: 97198 AN: 148482 Hom.: 32476 Cov.: 0 AF XY: 0.656 AC XY: 47269 AN XY: 72036

Gnomad4 AFR AF: 0.757

Gnomad4 AMR AF: 0.671

Gnomad4 ASJ AF: 0.698

Gnomad4 EAS AF: 0.830

Gnomad4 SAS AF: 0.653

Gnomad4 FIN AF: 0.590

Gnomad4 NFE AF: 0.585

Gnomad4 OTH AF: 0.677

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 12, 2021

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs67469465; hg19: chr2-84755996;