14-73689526-C-T

Position:

• chr14-73689526-C-T

Variant summary

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

The ENST00000553645.7(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 ENST00000553645.7 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.0360

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]

ACMG classification

Verdict is Benign. Variant got -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 id is 163172.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-73689526-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0634 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAL1	NM_031427.4	c.532+11C>T		intron_variant		ENST00000553645.7	NP_113615.2
DNAL1	NM_001201366.2	c.415+11C>T		intron_variant			NP_001188295.1
DNAL1	XM_017021679.3	c.415+11C>T		intron_variant			XP_016877168.1
DNAL1	XM_024449715.2	c.415+11C>T		intron_variant			XP_024305483.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAL1	ENST00000553645.7	c.532+11C>T		intron_variant		1	NM_031427.4	ENSP00000452037	P1

Frequencies

GnomAD3 genomes AF: 0.0461 AC: 7013 AN: 152042 Hom.: 202 Cov.: 31

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

GnomAD3 exomes AF: 0.0496 AC: 10282 AN: 207444 Hom.: 288 AF XY: 0.0501 AC XY: 5553 AN XY: 110738

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 SAS exome AF: 0.0337

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.: 32 AF XY: 0.0608 AC XY: 43164 AN XY: 710424

Gnomad4 AFR exome AF: 0.0102

Gnomad4 AMR exome AF: 0.0353

Gnomad4 ASJ exome AF: 0.0812

Gnomad4 EAS exome AF: 0.0290

Gnomad4 SAS exome AF: 0.0346

Gnomad4 FIN exome AF: 0.0376

Gnomad4 NFE exome AF: 0.0675

Gnomad4 OTH exome AF: 0.0606

GnomAD4 genome AF: 0.0461 AC: 7008 AN: 152160 Hom.: 202 Cov.: 31 AF XY: 0.0443 AC XY: 3297 AN XY: 74400

Gnomad4 AFR AF: 0.0119

Gnomad4 AMR AF: 0.0551

Gnomad4 ASJ AF: 0.0880

Gnomad4 EAS AF: 0.0375

Gnomad4 SAS AF: 0.0321

Gnomad4 FIN AF: 0.0374

Gnomad4 NFE AF: 0.0650

Gnomad4 OTH AF: 0.0620

Alfa AF: 0.0437 Hom.: 81

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

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Feb 21, 2013	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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Primary ciliary dyskinesia 16 Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	11
DANN	Benign	0.69

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: rs72721725; hg19: chr14-74156229;