rs114223887

Variant names:

• chr14-73689328-G-A
• rs114223887
• NM_031427.4:c.392-47G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_031427.4(DNAL1):​c.392-47G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0514 in 1,547,294 control chromosomes in the GnomAD database, including 2,243 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.046 (178 hom., cov: 30)
  • Exomes 𝑓: 0.052 (2065 hom.)
• Consequence: DNAL1 NM_031427.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.70
• Publications: 1 publications found

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BP6: Variant 14-73689328-G-A is Benign according to our data. Variant chr14-73689328-G-A is described in ClinVar as Benign. ClinVar VariationId is 261959.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0539 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031427.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAL1	NM_031427.4	MANE Select	c.392-47G>A		intron	N/A	NP_113615.2
	DNAL1	NM_001201366.2		c.275-47G>A		intron	N/A	NP_001188295.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAL1	ENST00000553645.7	TSL:1 MANE Select	c.392-47G>A		intron	N/A	ENSP00000452037.1
	DNAL1	ENST00000554871.5	TSL:1	c.275-47G>A		intron	N/A	ENSP00000451834.1
	DNAL1	ENST00000893991.1		c.391+1943G>A		intron	N/A	ENSP00000564050.1

Frequencies

GnomAD3 genomes AF: 0.0464 AC: 7051 AN: 152062 Hom.: 177 Cov.: 30

Gnomad AFR AF: 0.0559

Gnomad AMI AF: 0.00330

Gnomad AMR AF: 0.0315

Gnomad ASJ AF: 0.0331

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0446

Gnomad FIN AF: 0.0258

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0516

Gnomad OTH AF: 0.0536

GnomAD2 exomes AF: 0.0410 AC: 6390 AN: 155768 AF XY: 0.0430

Gnomad AFR exome AF: 0.0540

Gnomad AMR exome AF: 0.0263

Gnomad ASJ exome AF: 0.0340

Gnomad EAS exome AF: 0.000184

Gnomad FIN exome AF: 0.0263

Gnomad NFE exome AF: 0.0527

Gnomad OTH exome AF: 0.0470

GnomAD4 exome AF: 0.0520 AC: 72484 AN: 1395114 Hom.: 2065 Cov.: 31 AF XY: 0.0524 AC XY: 36019 AN XY: 687558

African (AFR) AF: 0.0552 AC: 1737 AN: 31470

American (AMR) AF: 0.0287 AC: 1022 AN: 35576

Ashkenazi Jewish (ASJ) AF: 0.0369 AC: 924 AN: 25066

East Asian (EAS) AF: 0.000168 AC: 6 AN: 35628

South Asian (SAS) AF: 0.0547 AC: 4322 AN: 78948

European-Finnish (FIN) AF: 0.0289 AC: 1413 AN: 48872

Middle Eastern (MID) AF: 0.0647 AC: 367 AN: 5676

European-Non Finnish (NFE) AF: 0.0556 AC: 59803 AN: 1076090

Other (OTH) AF: 0.0500 AC: 2890 AN: 57788

GnomAD4 genome AF: 0.0464 AC: 7055 AN: 152180 Hom.: 178 Cov.: 30 AF XY: 0.0455 AC XY: 3386 AN XY: 74406

African (AFR) AF: 0.0558 AC: 2315 AN: 41512

American (AMR) AF: 0.0314 AC: 480 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0331 AC: 115 AN: 3470

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5182

South Asian (SAS) AF: 0.0453 AC: 218 AN: 4816

European-Finnish (FIN) AF: 0.0258 AC: 273 AN: 10600

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0517 AC: 3513 AN: 68012

Other (OTH) AF: 0.0530 AC: 112 AN: 2112

Alfa AF: 0.0474 Hom.: 41

Bravo AF: 0.0451

Asia WGS AF: 0.0220 AC: 77 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.55
DANN	Benign	0.85
PhyloP100		-1.7
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

Other links and lift over

dbSNP: rs114223887; hg19: chr14-74156031;