2-84528872-ATTT-ATTTT

Variant names:

• chr2-84528872-A-AT
• rs67469465
• NM_001370.2:c.400-21dupT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001370.2(DNAH6):​c.400-21dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★). There are indicators that this mutation may affect the branch point..

• 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
• 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 -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 rank	MANE	Protein	UniProt
DNAH6	NM_001370.2	c.400-21dupT		intron_variant	Intron 3 of 76	ENST00000389394.8	NP_001361.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH6	ENST00000389394.8	c.400-32_400-31insT		intron_variant	Intron 3 of 76	5	NM_001370.2	ENSP00000374045.3
DNAH6	ENST00000494025.1	n.229+10821_229+10822insT		intron_variant	Intron 1 of 8	1
DNAH6	ENST00000468661.1	n.454+3134_454+3135insT		intron_variant	Intron 3 of 3	4
DNAH6	ENST00000476689.5	n.536+3134_536+3135insT		intron_variant	Intron 3 of 10	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

GnomAD2 exomes AF: 0.508 AC: 46245 AN: 91098 AF XY: 0.501

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 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

African (AFR) AF: 0.567 AC: 13604 AN: 24010

American (AMR) AF: 0.534 AC: 11554 AN: 21638

Ashkenazi Jewish (ASJ) AF: 0.526 AC: 10307 AN: 19610

East Asian (EAS) AF: 0.596 AC: 16596 AN: 27840

South Asian (SAS) AF: 0.487 AC: 29625 AN: 60890

European-Finnish (FIN) AF: 0.490 AC: 19489 AN: 39798

Middle Eastern (MID) AF: 0.605 AC: 2891 AN: 4776

European-Non Finnish (NFE) AF: 0.483 AC: 441152 AN: 913212

Other (OTH) AF: 0.508 AC: 24175 AN: 47604

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

African (AFR) AF: 0.757 AC: 30564 AN: 40380

American (AMR) AF: 0.671 AC: 10024 AN: 14928

Ashkenazi Jewish (ASJ) AF: 0.698 AC: 2410 AN: 3454

East Asian (EAS) AF: 0.830 AC: 4175 AN: 5028

South Asian (SAS) AF: 0.653 AC: 3021 AN: 4624

European-Finnish (FIN) AF: 0.590 AC: 5597 AN: 9482

Middle Eastern (MID) AF: 0.688 AC: 201 AN: 292

European-Non Finnish (NFE) AF: 0.585 AC: 39357 AN: 67318

Other (OTH) AF: 0.677 AC: 1402 AN: 2070

Alfa AF: 0.547 Hom.: 396

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 12, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.80
La Branchor		0.96
BranchPoint Hunter		6.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs67469465; hg19: chr2-84755996;