2-84528872-A-ATT

Variant summary

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

The NM_001370.2(DNAH6):c.400-22_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 0.24 (5262 hom., cov: 0)
  • Exomes 𝑓: 0.34 (16393 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-ATT is Benign according to our data. Variant chr2-84528872-A-ATT is described in ClinVar as [Benign]. Clinvar id is 1271750.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH6	NM_001370.2	c.400-22_400-21dup		intron_variant		ENST00000389394.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH6	ENST00000389394.8	c.400-22_400-21dup		intron_variant		5	NM_001370.2	P1
DNAH6	ENST00000494025.1	n.229+10831_229+10832dup		intron_variant, non_coding_transcript_variant		1
DNAH6	ENST00000468661.1	n.454+3144_454+3145dup		intron_variant, non_coding_transcript_variant		4
DNAH6	ENST00000476689.5	n.536+3144_536+3145dup		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.245 AC: 36274 AN: 148274 Hom.: 5261 Cov.: 0

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.415

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.165

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.333

Gnomad MID AF: 0.179

Gnomad NFE AF: 0.322

Gnomad OTH AF: 0.230

GnomAD3 exomes AF: 0.326 AC: 29680 AN: 91098 Hom.: 888 AF XY: 0.330 AC XY: 15950 AN XY: 48272

Gnomad AFR exome AF: 0.185

Gnomad AMR exome AF: 0.298

Gnomad ASJ exome AF: 0.341

Gnomad EAS exome AF: 0.308

Gnomad SAS exome AF: 0.317

Gnomad FIN exome AF: 0.359

Gnomad NFE exome AF: 0.346

Gnomad OTH exome AF: 0.327

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.343 AC: 374217 AN: 1091380 Hom.: 16393 Cov.: 33 AF XY: 0.343 AC XY: 183598 AN XY: 535828

Gnomad4 AFR exome AF: 0.166

Gnomad4 AMR exome AF: 0.294

Gnomad4 ASJ exome AF: 0.330

Gnomad4 EAS exome AF: 0.269

Gnomad4 SAS exome AF: 0.312

Gnomad4 FIN exome AF: 0.365

Gnomad4 NFE exome AF: 0.354

Gnomad4 OTH exome AF: 0.320

GnomAD4 genome AF: 0.245 AC: 36284 AN: 148358 Hom.: 5262 Cov.: 0 AF XY: 0.243 AC XY: 17520 AN XY: 71966

Gnomad4 AFR AF: 0.105

Gnomad4 AMR AF: 0.237

Gnomad4 ASJ AF: 0.250

Gnomad4 EAS AF: 0.165

Gnomad4 SAS AF: 0.236

Gnomad4 FIN AF: 0.333

Gnomad4 NFE AF: 0.322

Gnomad4 OTH AF: 0.231

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

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Computational scores

Source: dbNSFP v4.3

Splicing

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;