rs201880561

chr14-73661975-G-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_031427.4(DNAL1):c.153-12G>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 0.000736 in 1,533,590 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0039 (4 hom., cov: 32)
  • Exomes 𝑓: 0.00039 (4 hom.)
• Consequence: DNAL1 NM_031427.4 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00004958
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.16

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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 14-73661975-G-C is Benign according to our data. Variant chr14-73661975-G-C is described in ClinVar as [Benign]. Clinvar id is 261957.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-73661975-G-C is described in Lovd as [Likely_benign].
• BS2: High Homozygotes in GnomAd at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAL1	NM_031427.4	c.153-12G>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000553645.7
DNAL1	NM_001201366.2	c.36-12G>C		splice_polypyrimidine_tract_variant, intron_variant
DNAL1	XM_017021679.3	c.36-12G>C		splice_polypyrimidine_tract_variant, intron_variant
DNAL1	XM_024449715.2	c.36-12G>C		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAL1	ENST00000553645.7	c.153-12G>C		splice_polypyrimidine_tract_variant, intron_variant		1	NM_031427.4	P1

Frequencies

GnomAD3 genomes AF: 0.00390 AC: 593 AN: 151894 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.0136

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00144

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000442

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00109 AC: 164 AN: 150196 Hom.: 2 AF XY: 0.000835 AC XY: 66 AN XY: 79018

Gnomad AFR exome AF: 0.0168

Gnomad AMR exome AF: 0.00102

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000709

GnomAD4 exome AF: 0.000388 AC: 536 AN: 1381578 Hom.: 4 Cov.: 29 AF XY: 0.000325 AC XY: 221 AN XY: 680884

Gnomad4 AFR exome AF: 0.0138

Gnomad4 AMR exome AF: 0.00120

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000268

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000140

Gnomad4 OTH exome AF: 0.000820

GnomAD4 genome AF: 0.00390 AC: 593 AN: 152012 Hom.: 4 Cov.: 32 AF XY: 0.00367 AC XY: 273 AN XY: 74302

Gnomad4 AFR AF: 0.0136

Gnomad4 AMR AF: 0.00137

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000442

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00278 Hom.: 0

Bravo AF: 0.00478

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Primary ciliary dyskinesia 16 Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 14, 2024	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Aug 21, 2023	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
Cadd	Benign	11
Dann	Benign	0.84

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000050
dbscSNV1_RF	Benign	0.0040
SpliceAI score (max)		0.020		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: rs201880561; hg19: chr14-74128678;