chr2-84525506-A-C

Variant names:

• chr2-84525506-A-C
• rs9784108
• NM_001370.2:c.226-59A>C

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.226-59A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0302 in 1,486,364 control chromosomes in the GnomAD database, including 3,176 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.092 (1615 hom., cov: 32)
  • Exomes 𝑓: 0.023 (1561 hom.)
• Consequence: DNAH6 NM_001370.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.979

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

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 2-84525506-A-C is Benign according to our data. Variant chr2-84525506-A-C is described in ClinVar as [Benign]. Clinvar id is 1265934.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.272 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH6	NM_001370.2	c.226-59A>C		intron_variant	Intron 2 of 76	ENST00000389394.8	NP_001361.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH6	ENST00000389394.8	c.226-59A>C		intron_variant	Intron 2 of 76	5	NM_001370.2	ENSP00000374045.3
DNAH6	ENST00000494025.1	n.229+7455A>C		intron_variant	Intron 1 of 8	1
DNAH6	ENST00000468661.1	n.281-59A>C		intron_variant	Intron 2 of 3	4
DNAH6	ENST00000476689.5	n.363-59A>C		intron_variant	Intron 2 of 10	2

Frequencies

GnomAD3 genomes AF: 0.0919 AC: 13971 AN: 152000 Hom.: 1613 Cov.: 32

Gnomad AFR AF: 0.277

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0535

Gnomad ASJ AF: 0.0479

Gnomad EAS AF: 0.0112

Gnomad SAS AF: 0.0595

Gnomad FIN AF: 0.00396

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0139

Gnomad OTH AF: 0.0809

GnomAD4 exome AF: 0.0231 AC: 30840 AN: 1334246 Hom.: 1561 AF XY: 0.0240 AC XY: 15810 AN XY: 659822

African (AFR) AF: 0.282 AC: 8020 AN: 28438

American (AMR) AF: 0.0370 AC: 910 AN: 24604

Ashkenazi Jewish (ASJ) AF: 0.0514 AC: 1208 AN: 23516

East Asian (EAS) AF: 0.0209 AC: 737 AN: 35260

South Asian (SAS) AF: 0.0610 AC: 4361 AN: 71448

European-Finnish (FIN) AF: 0.00498 AC: 243 AN: 48790

Middle Eastern (MID) AF: 0.0812 AC: 419 AN: 5160

European-Non Finnish (NFE) AF: 0.0122 AC: 12720 AN: 1041558

Other (OTH) AF: 0.0401 AC: 2222 AN: 55472

GnomAD4 genome AF: 0.0920 AC: 13992 AN: 152118 Hom.: 1615 Cov.: 32 AF XY: 0.0891 AC XY: 6627 AN XY: 74374

African (AFR) AF: 0.276 AC: 11464 AN: 41462

American (AMR) AF: 0.0534 AC: 815 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.0479 AC: 166 AN: 3468

East Asian (EAS) AF: 0.0112 AC: 58 AN: 5172

South Asian (SAS) AF: 0.0592 AC: 285 AN: 4818

European-Finnish (FIN) AF: 0.00396 AC: 42 AN: 10616

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.0139 AC: 945 AN: 68004

Other (OTH) AF: 0.0814 AC: 172 AN: 2112

Alfa AF: 0.0671 Hom.: 135

Bravo AF: 0.102

Asia WGS AF: 0.0550 AC: 191 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

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

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	13
DANN	Benign	0.63
PhyloP100		0.98
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

Publications

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Other links and lift over

dbSNP: rs9784108; hg19: chr2-84752630;