rs11676670

chr2-84624887-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001370.2(DNAH6):c.4354-15C>T variant causes a splice polypyrimidine tract, 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 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.379

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 -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 id 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/exons	MANE	UniProt
DNAH6	NM_001370.2	c.4354-15C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000389394.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH6	ENST00000389394.8	c.4354-15C>T		splice_polypyrimidine_tract_variant, intron_variant		5	NM_001370.2	P1

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

GnomAD3 exomes AF: 0.0941 AC: 13591 AN: 144486 Hom.: 1224 AF XY: 0.0906 AC XY: 6891 AN XY: 76060

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 SAS exome AF: 0.114

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

Gnomad4 AFR exome AF: 0.448

Gnomad4 AMR exome AF: 0.0775

Gnomad4 ASJ exome AF: 0.0667

Gnomad4 EAS exome AF: 0.0219

Gnomad4 SAS exome AF: 0.111

Gnomad4 FIN exome AF: 0.0468

Gnomad4 NFE exome AF: 0.0781

Gnomad4 OTH exome AF: 0.105

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

Gnomad4 AFR AF: 0.438

Gnomad4 AMR AF: 0.120

Gnomad4 ASJ AF: 0.0637

Gnomad4 EAS AF: 0.0141

Gnomad4 SAS AF: 0.111

Gnomad4 FIN AF: 0.0511

Gnomad4 NFE AF: 0.0782

Gnomad4 OTH AF: 0.160

Alfa AF: 0.112 Hom.: 635

Bravo AF: 0.192

Asia WGS AF: 0.0900 AC: 312 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

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 -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 11, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	2.3
Dann	Benign	0.31

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

Publications

LitVar

Other links and lift over

dbSNP: rs11676670; hg19: chr2-84852011;