2-84528872-ATTT-ATTTTT

Variant names:

• chr2-84528872-A-ATT
• rs67469465
• NM_001370.2:c.400-22_400-21dupTT

Variant summary

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

The NM_001370.2(DNAH6):​c.400-22_400-21dupTT 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 0.24 (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
• 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-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 rank	MANE	Protein	UniProt
DNAH6	NM_001370.2	c.400-22_400-21dupTT		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_400-31insTT		intron_variant	Intron 3 of 76	5	NM_001370.2	ENSP00000374045.3
DNAH6	ENST00000494025.1	n.229+10821_229+10822insTT		intron_variant	Intron 1 of 8	1
DNAH6	ENST00000468661.1	n.454+3134_454+3135insTT		intron_variant	Intron 3 of 3	4
DNAH6	ENST00000476689.5	n.536+3134_536+3135insTT		intron_variant	Intron 3 of 10	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

GnomAD2 exomes AF: 0.326 AC: 29680 AN: 91098 AF XY: 0.330

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 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

African (AFR) AF: 0.166 AC: 3522 AN: 21204

American (AMR) AF: 0.294 AC: 5829 AN: 19812

Ashkenazi Jewish (ASJ) AF: 0.330 AC: 5935 AN: 17972

East Asian (EAS) AF: 0.269 AC: 6169 AN: 22946

South Asian (SAS) AF: 0.312 AC: 17849 AN: 57278

European-Finnish (FIN) AF: 0.365 AC: 13844 AN: 37958

Middle Eastern (MID) AF: 0.212 AC: 952 AN: 4482

European-Non Finnish (NFE) AF: 0.354 AC: 306019 AN: 865662

Other (OTH) AF: 0.320 AC: 14098 AN: 44066

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

African (AFR) AF: 0.105 AC: 4221 AN: 40354

American (AMR) AF: 0.237 AC: 3537 AN: 14910

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 863 AN: 3454

East Asian (EAS) AF: 0.165 AC: 827 AN: 5022

South Asian (SAS) AF: 0.236 AC: 1093 AN: 4632

European-Finnish (FIN) AF: 0.333 AC: 3133 AN: 9416

Middle Eastern (MID) AF: 0.188 AC: 55 AN: 292

European-Non Finnish (NFE) AF: 0.322 AC: 21701 AN: 67302

Other (OTH) AF: 0.231 AC: 478 AN: 2070

Alfa AF: 0.329 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

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs67469465; hg19: chr2-84755996;