14-73654832-T-C

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_031427.4(DNAL1):c.4-15T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00224 in 1,507,920 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0020 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0023 (5 hom.)
• Consequence: DNAL1 NM_031427.4 splice_polypyrimidine_tract, intron
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: 0.877

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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 14-73654832-T-C is Benign according to our data. Variant chr14-73654832-T-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 195386.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=1}.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAL1	NM_031427.4	c.4-15T>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000553645.7
DNAL1	NM_001201366.2	c.-114-15T>C		splice_polypyrimidine_tract_variant, intron_variant
DNAL1	XM_017021679.3	c.-114-15T>C		splice_polypyrimidine_tract_variant, intron_variant
DNAL1	XM_024449715.2	c.-114-15T>C		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAL1	ENST00000553645.7	c.4-15T>C		splice_polypyrimidine_tract_variant, intron_variant		1	NM_031427.4	P1

Frequencies

GnomAD3 genomes AF: 0.00204 AC: 309 AN: 151704 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000387

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.00197

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00365

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00271

Gnomad OTH AF: 0.00478

GnomAD3 exomes AF: 0.00211 AC: 247 AN: 117202 Hom.: 1 AF XY: 0.00210 AC XY: 131 AN XY: 62488

Gnomad AFR exome AF: 0.000441

Gnomad AMR exome AF: 0.00218

Gnomad ASJ exome AF: 0.000726

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00135

Gnomad FIN exome AF: 0.00332

Gnomad NFE exome AF: 0.00276

Gnomad OTH exome AF: 0.00251

GnomAD4 exome AF: 0.00227 AC: 3076 AN: 1356098 Hom.: 5 Cov.: 33 AF XY: 0.00222 AC XY: 1483 AN XY: 668586

Gnomad4 AFR exome AF: 0.000310

Gnomad4 AMR exome AF: 0.00208

Gnomad4 ASJ exome AF: 0.00100

Gnomad4 EAS exome AF: 0.0000283

Gnomad4 SAS exome AF: 0.00153

Gnomad4 FIN exome AF: 0.00403

Gnomad4 NFE exome AF: 0.00244

Gnomad4 OTH exome AF: 0.00189

GnomAD4 genome AF: 0.00204 AC: 309 AN: 151822 Hom.: 2 Cov.: 32 AF XY: 0.00191 AC XY: 142 AN XY: 74218

Gnomad4 AFR AF: 0.000386

Gnomad4 AMR AF: 0.00197

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00365

Gnomad4 NFE AF: 0.00271

Gnomad4 OTH AF: 0.00473

Alfa AF: 0.00270 Hom.: 0

Bravo AF: 0.00176

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:1

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Jul 22, 2014

- -

Primary ciliary dyskinesia 16 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 28, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.36
Dann	Benign	0.50

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

Publications

LitVar

Other links and lift over

dbSNP: rs185924269; hg19: chr14-74121535;