chr14-73687394-A-G

Variant names:

• chr14-73687394-A-G
• rs149911093
• NM_031427.4:c.391+9A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 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: DEFINITIVE, STRONG, MODERATE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 11 AR,AD gene

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.391+9A>G		intron	N/A	NP_113615.2	Q4LDG9-1
	DNAL1	NM_001201366.2		c.274+9A>G		intron	N/A	NP_001188295.1	Q4LDG9-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAL1	ENST00000553645.7	TSL:1 MANE Select	c.391+9A>G		intron	N/A	ENSP00000452037.1	Q4LDG9-1
	DNAL1	ENST00000554871.5	TSL:1	c.274+9A>G		intron	N/A	ENSP00000451834.1	Q4LDG9-3
	DNAL1	ENST00000893991.1		c.391+9A>G		intron	N/A	ENSP00000564050.1

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

GnomAD2 exomes AF: 0.00166 AC: 374 AN: 224912 AF XY: 0.00141

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 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

African (AFR) AF: 0.0216 AC: 688 AN: 31780

American (AMR) AF: 0.00108 AC: 42 AN: 38854

Ashkenazi Jewish (ASJ) AF: 0.0000404 AC: 1 AN: 24776

East Asian (EAS) AF: 0.00 AC: 0 AN: 38978

South Asian (SAS) AF: 0.0000379 AC: 3 AN: 79212

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52554

Middle Eastern (MID) AF: 0.00143 AC: 8 AN: 5590

European-Non Finnish (NFE) AF: 0.0000219 AC: 24 AN: 1094950

Other (OTH) AF: 0.00140 AC: 82 AN: 58672

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

African (AFR) AF: 0.0215 AC: 895 AN: 41548

American (AMR) AF: 0.00269 AC: 41 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68028

Other (OTH) AF: 0.00189 AC: 4 AN: 2114

Alfa AF: 0.00491 Hom.: 4

Bravo AF: 0.00695

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Primary ciliary dyskinesia 16 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	22
DANN	Benign	0.72
PhyloP100		2.4
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs149911093; hg19: chr14-74154097;