14-73689526-C-T

Variant names:

• chr14-73689526-C-T
• rs72721725
• NM_031427.4:c.532+11C>T

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.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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.0360
• Publications: 5 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 -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.

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.532+11C>T		intron	N/A	NP_113615.2	Q4LDG9-1
	DNAL1	NM_001201366.2		c.415+11C>T		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.532+11C>T		intron	N/A	ENSP00000452037.1	Q4LDG9-1
	DNAL1	ENST00000554871.5	TSL:1	c.415+11C>T		intron	N/A	ENSP00000451834.1	Q4LDG9-3
	DNAL1	ENST00000893991.1		c.391+2141C>T		intron	N/A	ENSP00000564050.1

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

GnomAD2 exomes AF: 0.0496 AC: 10282 AN: 207444 AF XY: 0.0501

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

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

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

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: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0650 AC: 4417 AN: 67980

Other (OTH) AF: 0.0620 AC: 131 AN: 2112

Alfa AF: 0.0437 Hom.: 81

Bravo AF: 0.0464

Asia WGS AF: 0.0450 AC: 159 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	1	Primary ciliary dyskinesia 16 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	11
DANN	Benign	0.69
PhyloP100		0.036
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: rs72721725; hg19: chr14-74156229;