rs540475697

Variant names:

• chr14-73654765-AATACATACATAC-A
• rs540475697
• NM_031427.4:c.4-67_4-56delACATACATACAT

Your query was ambiguous. Multiple possible variants found:

• chr14-73654765-AATACATACATAC-A
• chr14-73654765-AATACATACATAC-AATAC
• chr14-73654765-AATACATACATAC-AATACATAC
• chr14-73654765-AATACATACATAC-AATACATACATACATAC
• chr14-73654765-AATACATACATAC-AATACATACATACATACATAC

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_031427.4(DNAL1):​c.4-67_4-56delACATACATACAT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00296 in 1,287,512 control chromosomes in the GnomAD database, including 12 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0022 (2 hom., cov: 31)
  • Exomes 𝑓: 0.0031 (10 hom.)
• Consequence: DNAL1 NM_031427.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.933
• 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 -8 ACMG points.

• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00223 (338/151764) while in subpopulation AMR AF = 0.00544 (83/15250). AF 95% confidence interval is 0.0045. There are 2 homozygotes in GnomAd4. There are 158 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 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.4-67_4-56delACATACATACAT		intron	N/A	NP_113615.2	Q4LDG9-1
	DNAL1	NM_001201366.2		c.-114-67_-114-56delACATACATACAT		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.4-81_4-70delATACATACATAC		intron	N/A	ENSP00000452037.1	Q4LDG9-1
	DNAL1	ENST00000554871.5	TSL:1	c.-114-81_-114-70delATACATACATAC		intron	N/A	ENSP00000451834.1	Q4LDG9-3
	DNAL1	ENST00000893991.1		c.4-81_4-70delATACATACATAC		intron	N/A	ENSP00000564050.1

Frequencies

GnomAD3 genomes AF: 0.00223 AC: 338 AN: 151658 Hom.: 2 Cov.: 31

Gnomad AFR AF: 0.000752

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00545

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0000953

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00319

Gnomad OTH AF: 0.00240

GnomAD4 exome AF: 0.00305 AC: 3469 AN: 1135748 Hom.: 10 AF XY: 0.00304 AC XY: 1706 AN XY: 561812

African (AFR) AF: 0.000395 AC: 9 AN: 22798

American (AMR) AF: 0.00298 AC: 57 AN: 19098

Ashkenazi Jewish (ASJ) AF: 0.000511 AC: 10 AN: 19564

East Asian (EAS) AF: 0.0000309 AC: 1 AN: 32342

South Asian (SAS) AF: 0.0000672 AC: 4 AN: 59490

European-Finnish (FIN) AF: 0.000160 AC: 5 AN: 31210

Middle Eastern (MID) AF: 0.000879 AC: 3 AN: 3414

European-Non Finnish (NFE) AF: 0.00358 AC: 3224 AN: 900212

Other (OTH) AF: 0.00328 AC: 156 AN: 47620

GnomAD4 genome AF: 0.00223 AC: 338 AN: 151764 Hom.: 2 Cov.: 31 AF XY: 0.00213 AC XY: 158 AN XY: 74168

African (AFR) AF: 0.000750 AC: 31 AN: 41320

American (AMR) AF: 0.00544 AC: 83 AN: 15250

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4812

European-Finnish (FIN) AF: 0.0000953 AC: 1 AN: 10498

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00319 AC: 217 AN: 67932

Other (OTH) AF: 0.00238 AC: 5 AN: 2098

Alfa AF: 0.00128 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.93
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs540475697; hg19: chr14-74121468;