rs149911093

Positions:

• chr14-73687394-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_031427.4(DNAL1):​c.391+9A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00114 in 1,577,616 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0062 (11 hom., cov: 32)
  • Exomes 𝑓: 0.00059 (5 hom.)
• Consequence: DNAL1 NM_031427.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.45

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 -10 ACMG points.

• BP6: Variant 14-73687394-A-G is Benign according to our data. Variant chr14-73687394-A-G is described in ClinVar as [Benign]. Clinvar id is 241618.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00625 (951/152250) while in subpopulation AFR AF= 0.0215 (895/41548). AF 95% confidence interval is 0.0204. There are 11 homozygotes in gnomad4. There are 434 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAL1	NM_031427.4	c.391+9A>G		intron_variant		ENST00000553645.7
DNAL1	NM_001201366.2	c.274+9A>G		intron_variant
DNAL1	XM_017021679.3	c.274+9A>G		intron_variant
DNAL1	XM_024449715.2	c.274+9A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAL1	ENST00000553645.7	c.391+9A>G		intron_variant		1	NM_031427.4	P1

Frequencies

GnomAD3 genomes AF: 0.00624 AC: 949 AN: 152132 Hom.: 11 Cov.: 32

Gnomad AFR AF: 0.0216

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00269

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.00166 AC: 374 AN: 224912 Hom.: 1 AF XY: 0.00141 AC XY: 173 AN XY: 122350

Gnomad AFR exome AF: 0.0225

Gnomad AMR exome AF: 0.00108

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000789

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000946

Gnomad OTH exome AF: 0.000566

GnomAD4 exome AF: 0.000595 AC: 848 AN: 1425366 Hom.: 5 Cov.: 30 AF XY: 0.000487 AC XY: 344 AN XY: 706636

Gnomad4 AFR exome AF: 0.0216

Gnomad4 AMR exome AF: 0.00108

Gnomad4 ASJ exome AF: 0.0000404

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000379

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000219

Gnomad4 OTH exome AF: 0.00140

GnomAD4 genome AF: 0.00625 AC: 951 AN: 152250 Hom.: 11 Cov.: 32 AF XY: 0.00583 AC XY: 434 AN XY: 74442

Gnomad4 AFR AF: 0.0215

Gnomad4 AMR AF: 0.00269

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000132

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00507 Hom.: 2

Bravo AF: 0.00695

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Primary ciliary dyskinesia 16 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 26, 2024

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	22
DANN	Benign	0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.23		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.23		Position offset: -22

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs149911093; hg19: chr14-74154097;