dbSNP rs150636700: DNAL1:p.Glu164Glu (chr14-73689475-A-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7

The NM_031427.4(DNAL1):c.492A>G(p.Glu164Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000417 in 1,582,692 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000028 ( 0 hom. )

Consequence

DNAL1
NM_031427.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -2.81

Publications

2 publications found

Variant links:

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

DNAL1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 14-73689475-A-G is Benign according to our data. Variant chr14-73689475-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 241619.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.81 with no splicing effect.

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.492A>G	p.Glu164Glu	synonymous	Exon 7 of 8	NP_113615.2	Q4LDG9-1
	DNAL1	NM_001201366.2		c.375A>G	p.Glu125Glu	synonymous	Exon 8 of 9	NP_001188295.1	Q4LDG9-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DNAL1	ENST00000553645.7	TSL:1 MANE Select	c.492A>G	p.Glu164Glu	synonymous	Exon 7 of 8	ENSP00000452037.1	Q4LDG9-1
DNAL1	ENST00000554871.5	TSL:1	c.375A>G	p.Glu125Glu	synonymous	Exon 8 of 9	ENSP00000451834.1	Q4LDG9-3
DNAL1	ENST00000555631.6	TSL:4	c.375A>G	p.Glu125Glu	synonymous	Exon 8 of 8	ENSP00000451547.2	G3V424

Frequencies

GnomAD3 genomes

AF:

0.000164

AC:

AN:

152248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000531

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000442

AC:

AN:

203402

AF XY:

0.00000922

show subpopulations

Gnomad AFR exome

AF:

0.000416

Gnomad AMR exome

AF:

0.000138

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000280

AC:

AN:

1430326

Hom.:

Cov.:

AF XY:

0.0000169

AC XY:

AN XY:

708066

show subpopulations

African (AFR)

AF:

0.000548

AC:

AN:

32854

American (AMR)

AF:

0.000152

AC:

AN:

39520

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25508

East Asian (EAS)

AF:

0.00

AC:

AN:

38580

South Asian (SAS)

AF:

0.0000123

AC:

AN:

81152

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51666

Middle Eastern (MID)

AF:

0.000349

AC:

AN:

5736

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1095964

Other (OTH)

AF:

0.000219

AC:

AN:

59346

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000171

AC:

AN:

152366

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74504

show subpopulations

African (AFR)

AF:

0.000553

AC:

AN:

41588

American (AMR)

AF:

0.000196

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68036

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000203

Hom.:

Bravo

AF:

0.000200

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

not specified (1)

Primary ciliary dyskinesia 16 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

3.3

(source)

DANN

Benign

0.55

PhyloP100

-2.8

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over