rs11676670

Variant names:

• chr2-84624887-C-T
• rs11676670
• NM_001370.2:c.4354-15C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001370.2(DNAH6):​c.4354-15C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0958 in 1,536,130 control chromosomes in the GnomAD database, including 12,300 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.18 (4540 hom., cov: 33)
  • Exomes 𝑓: 0.087 (7760 hom.)
• Consequence: DNAH6 NM_001370.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.379
• Publications: 6 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 2-84624887-C-T is Benign according to our data. Variant chr2-84624887-C-T is described in ClinVar as Benign. ClinVar VariationId is 402736.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.433 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH6	NM_001370.2	c.4354-15C>T		intron_variant	Intron 28 of 76	ENST00000389394.8	NP_001361.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH6	ENST00000389394.8	c.4354-15C>T		intron_variant	Intron 28 of 76	5	NM_001370.2	ENSP00000374045.3

Frequencies

GnomAD3 genomes AF: 0.178 AC: 27112 AN: 151980 Hom.: 4523 Cov.: 33

Gnomad AFR AF: 0.438

Gnomad AMI AF: 0.0998

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.0637

Gnomad EAS AF: 0.0140

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.0511

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.0782

Gnomad OTH AF: 0.160

GnomAD2 exomes AF: 0.0941 AC: 13591 AN: 144486 AF XY: 0.0906

Gnomad AFR exome AF: 0.447

Gnomad AMR exome AF: 0.0724

Gnomad ASJ exome AF: 0.0689

Gnomad EAS exome AF: 0.0107

Gnomad FIN exome AF: 0.0479

Gnomad NFE exome AF: 0.0790

Gnomad OTH exome AF: 0.0888

GnomAD4 exome AF: 0.0868 AC: 120065 AN: 1384032 Hom.: 7760 Cov.: 31 AF XY: 0.0867 AC XY: 59088 AN XY: 681508

African (AFR) AF: 0.448 AC: 13834 AN: 30890

American (AMR) AF: 0.0775 AC: 2564 AN: 33064

Ashkenazi Jewish (ASJ) AF: 0.0667 AC: 1606 AN: 24092

East Asian (EAS) AF: 0.0219 AC: 778 AN: 35570

South Asian (SAS) AF: 0.111 AC: 8448 AN: 76190

European-Finnish (FIN) AF: 0.0468 AC: 2290 AN: 48922

Middle Eastern (MID) AF: 0.133 AC: 740 AN: 5562

European-Non Finnish (NFE) AF: 0.0781 AC: 83769 AN: 1072344

Other (OTH) AF: 0.105 AC: 6036 AN: 57398

GnomAD4 genome AF: 0.179 AC: 27172 AN: 152098 Hom.: 4540 Cov.: 33 AF XY: 0.175 AC XY: 12990 AN XY: 74374

African (AFR) AF: 0.438 AC: 18169 AN: 41446

American (AMR) AF: 0.120 AC: 1836 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0637 AC: 221 AN: 3470

East Asian (EAS) AF: 0.0141 AC: 73 AN: 5184

South Asian (SAS) AF: 0.111 AC: 533 AN: 4822

European-Finnish (FIN) AF: 0.0511 AC: 541 AN: 10584

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.0782 AC: 5318 AN: 68000

Other (OTH) AF: 0.160 AC: 337 AN: 2110

Alfa AF: 0.117 Hom.: 963

Bravo AF: 0.192

Asia WGS AF: 0.0900 AC: 312 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

May 11, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.3
DANN	Benign	0.31
PhyloP100		0.38
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11676670; hg19: chr2-84852011;