14-73689526-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_031427.4(DNAL1):c.532+11C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.06 in 1,586,552 control chromosomes in the GnomAD database, including 3,111 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.046 ( 202 hom., cov: 31)

Exomes 𝑓: 0.061 ( 2909 hom. )

Consequence

DNAL1
NM_031427.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.0360

Publications

5 publications found

Variant links:

Genes affected

DNAL1 (HGNC:23247): (dynein axonemal light chain 1) This gene encodes an axonemal dynein light chain which functions as a component of the outer dynein arms complex. This complex acts as the molecular motor that provides the force to move cilia in an ATP-dependent manner. The encoded protein is expressed in tissues with motile cilia or flagella and may be involved in the movement of sperm flagella. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Jan 2011]

DNAL1 Gene-Disease associations (from GenCC):

primary ciliary dyskinesia 16
Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: PanelApp Australia, Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)
primary ciliary dyskinesia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

DNAL1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BP6

Variant 14-73689526-C-T is Benign according to our data. Variant chr14-73689526-C-T is described in ClinVar as Benign. ClinVar VariationId is 163172.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0634 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
DNAL1	NM_031427.4 link	c.532+11C>T	intron_variant	Intron 7 of 7	ENST00000553645.7	NP_113615.2
DNAL1	NM_001201366.2 link	c.415+11C>T	intron_variant	Intron 8 of 8		NP_001188295.1
DNAL1	XM_017021679.3 link	c.415+11C>T	intron_variant	Intron 8 of 8		XP_016877168.1
DNAL1	XM_024449715.2 link	c.415+11C>T	intron_variant	Intron 8 of 8		XP_024305483.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAL1	ENST00000553645.7 link	c.532+11C>T		intron_variant	Intron 7 of 7	1	NM_031427.4	ENSP00000452037.1

Frequencies

GnomAD3 genomes

AF:

0.0461

AC:

7013

AN:

152042

Hom.:

202

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0119

Gnomad AMI

AF:

0.0559

Gnomad AMR

AF:

0.0553

Gnomad ASJ

AF:

0.0880

Gnomad EAS

AF:

0.0374

Gnomad SAS

AF:

0.0319

Gnomad FIN

AF:

0.0374

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.0650

Gnomad OTH

AF:

0.0627

GnomAD2 exomes

AF:

0.0496

AC:

10282

AN:

207444

AF XY:

0.0501

show subpopulations

Gnomad AFR exome

AF:

0.0107

Gnomad AMR exome

AF:

0.0347

Gnomad ASJ exome

AF:

0.0787

Gnomad EAS exome

AF:

0.0327

Gnomad FIN exome

AF:

0.0383

Gnomad NFE exome

AF:

0.0657

Gnomad OTH exome

AF:

0.0601

GnomAD4 exome

AF:

0.0615

AC:

88178

AN:

1434392

Hom.:

2909

Cov.:

AF XY:

0.0608

AC XY:

43164

AN XY:

710424

show subpopulations

African (AFR)

AF:

0.0102

AC:

337

AN:

32980

American (AMR)

AF:

0.0353

AC:

1421

AN:

40210

Ashkenazi Jewish (ASJ)

AF:

0.0812

AC:

2075

AN:

25546

East Asian (EAS)

AF:

0.0290

AC:

1125

AN:

38788

South Asian (SAS)

AF:

0.0346

AC:

2821

AN:

81624

European-Finnish (FIN)

AF:

0.0376

AC:

1949

AN:

51864

Middle Eastern (MID)

AF:

0.117

AC:

672

AN:

5738

European-Non Finnish (NFE)

AF:

0.0675

AC:

74173

AN:

1098112

Other (OTH)

AF:

0.0606

AC:

3605

AN:

59530

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

4474

8947

13421

17894

22368

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2772

5544

8316

11088

13860

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0461

AC:

7008

AN:

152160

Hom.:

202

Cov.:

AF XY:

0.0443

AC XY:

3297

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.0119

AC:

493

AN:

41534

American (AMR)

AF:

0.0551

AC:

842

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.0880

AC:

305

AN:

3466

East Asian (EAS)

AF:

0.0375

AC:

194

AN:

5180

South Asian (SAS)

AF:

0.0321

AC:

155

AN:

4824

European-Finnish (FIN)

AF:

0.0374

AC:

396

AN:

10576

Middle Eastern (MID)

AF:

0.0816

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0650

AC:

4417

AN:

67980

Other (OTH)

AF:

0.0620

AC:

131

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

336

671

1007

1342

1678

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

156

234

312

390

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0437

Hom.:

Bravo

AF:

0.0464

Asia WGS

AF:

0.0450

AC:

159

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Feb 21, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

415+11C>T in intron 8 of DNAL1: This variant is not expected to have clinical si gnificance because it is not located within the conserved splice consensus seque nce. It has been identified in 6.5% (537/8256) of European American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.was hington.edu/EVS; dbSNP rs72721725).

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Nov 10, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Primary ciliary dyskinesia 16

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

(source)

DANN

Benign

0.69

PhyloP100

0.036

Mutation Taster

=100/0

polymorphism (auto)

(source)

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over