14-73654824-CTTTCT-C

Variant names:

• chr14-73654824-CTTTCT-C
• NM_031427.4:c.4-19_4-15delCTTTT

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_031427.4(DNAL1):​c.4-19_4-15delCTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000447 in 1,342,068 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000045 (0 hom.)
• Consequence: DNAL1 NM_031427.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.588

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 14-73654824-CTTTCT-C is Benign according to our data. Variant chr14-73654824-CTTTCT-C is described in ClinVar as [Likely_benign]. Clinvar id is 3714081.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAL1	NM_031427.4	c.4-19_4-15delCTTTT		intron_variant	Intron 1 of 7	ENST00000553645.7	NP_113615.2
DNAL1	NM_001201366.2	c.-114-19_-114-15delCTTTT		intron_variant	Intron 2 of 8		NP_001188295.1
DNAL1	XM_017021679.3	c.-114-19_-114-15delCTTTT		intron_variant	Intron 2 of 8		XP_016877168.1
DNAL1	XM_024449715.2	c.-114-19_-114-15delCTTTT		intron_variant	Intron 2 of 8		XP_024305483.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAL1	ENST00000553645.7	c.4-22_4-18delTTTCT		intron_variant	Intron 1 of 7	1	NM_031427.4	ENSP00000452037.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000447 AC: 6 AN: 1342068 Hom.: 0 AF XY: 0.00000453 AC XY: 3 AN XY: 662270

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000283

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000474

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Primary ciliary dyskinesia 16 Benign:1

Jun 03, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-74121527;