chr14-73654824-CTTTCT-C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. 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
• 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: Likely_benign. The variant received -2 ACMG points.

• 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 VariationId is 3714081.Status of the report is criteria_provided_single_submitter, 1 stars.

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.4-19_4-15delCTTTT		intron	N/A	NP_113615.2	Q4LDG9-1
	DNAL1	NM_001201366.2		c.-114-19_-114-15delCTTTT		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.4-22_4-18delTTTCT		intron	N/A	ENSP00000452037.1	Q4LDG9-1
	DNAL1	ENST00000554871.5	TSL:1	c.-114-22_-114-18delTTTCT		intron	N/A	ENSP00000451834.1	Q4LDG9-3
	DNAL1	ENST00000893991.1		c.4-22_4-18delTTTCT		intron	N/A	ENSP00000564050.1

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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 28688

American (AMR) AF: 0.00 AC: 0 AN: 25614

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23762

East Asian (EAS) AF: 0.0000283 AC: 1 AN: 35332

South Asian (SAS) AF: 0.00 AC: 0 AN: 71590

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40432

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5066

European-Non Finnish (NFE) AF: 0.00000474 AC: 5 AN: 1055844

Other (OTH) AF: 0.00 AC: 0 AN: 55740

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Primary ciliary dyskinesia 16 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.59

Splicing

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

Other links and lift over

hg19: chr14-74121527;