22-38782696-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_005740.3(DNAL4):c.36T>C(p.Asp12Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 1,611,918 control chromosomes in the GnomAD database, including 84,416 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.33 ( 8650 hom., cov: 32)

Exomes 𝑓: 0.31 ( 75766 hom. )

Consequence

DNAL4
NM_005740.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.248

Publications

22 publications found

Variant links:

Genes affected

DNAL4 (HGNC:2955): (dynein axonemal light chain 4) 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. [provided by RefSeq, Dec 2014]

DNAL4 links:

SUN2 (HGNC:14210): (Sad1 and UNC84 domain containing 2) SUN1 (MIM 607723) and SUN2 are inner nuclear membrane (INM) proteins that play a major role in nuclear-cytoplasmic connection by formation of a 'bridge' across the nuclear envelope, known as the LINC complex, via interaction with the conserved luminal KASH domain of nesprins (e.g., SYNE1; MIM 608441) located in the outer nuclear membrane (ONM). The LINC complex provides a direct connection between the nuclear lamina and the cytoskeleton, which contributes to nuclear positioning and cellular rigidity (summary by Haque et al., 2010 [PubMed 19933576]).[supplied by OMIM, Nov 2010]

SUN2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

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

BP6

Variant 22-38782696-A-G is Benign according to our data. Variant chr22-38782696-A-G is described in ClinVar as [Benign]. Clinvar id is 402791.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.248 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.657 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAL4	NM_005740.3 link	c.36T>C	p.Asp12Asp	synonymous_variant	Exon 2 of 4	ENST00000216068.9	NP_005731.1	O96015

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DNAL4	ENST00000216068.9 link	c.36T>C	p.Asp12Asp	synonymous_variant	Exon 2 of 4	1	NM_005740.3	ENSP00000216068.4	O96015
DNAL4	ENST00000406199.3 link	c.36T>C	p.Asp12Asp	synonymous_variant	Exon 2 of 3	2		ENSP00000385712.3	B0QXZ5
SUN2	ENST00000406622.5 link	c.-138+11372T>C		intron_variant	Intron 1 of 18	2		ENSP00000383992.1	Q9UH99-1
DNAL4	ENST00000486019.1 link	n.82-3083T>C		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes

AF:

0.327

AC:

49754

AN:

151994

Hom.:

8655

Cov.:

show subpopulations

Gnomad AFR

AF:

0.375

Gnomad AMI

AF:

0.335

Gnomad AMR

AF:

0.246

Gnomad ASJ

AF:

0.268

Gnomad EAS

AF:

0.676

Gnomad SAS

AF:

0.393

Gnomad FIN

AF:

0.223

Gnomad MID

AF:

0.266

Gnomad NFE

AF:

0.306

Gnomad OTH

AF:

0.300

GnomAD2 exomes

AF:

0.322

AC:

80391

AN:

249842

AF XY:

0.327

show subpopulations

Gnomad AFR exome

AF:

0.375

Gnomad AMR exome

AF:

0.187

Gnomad ASJ exome

AF:

0.266

Gnomad EAS exome

AF:

0.687

Gnomad FIN exome

AF:

0.230

Gnomad NFE exome

AF:

0.303

Gnomad OTH exome

AF:

0.299

GnomAD4 exome

AF:

0.313

AC:

457437

AN:

1459806

Hom.:

75766

Cov.:

AF XY:

0.316

AC XY:

229226

AN XY:

726264

show subpopulations

African (AFR)

AF:

0.380

AC:

12662

AN:

33350

American (AMR)

AF:

0.193

AC:

8572

AN:

44478

Ashkenazi Jewish (ASJ)

AF:

0.264

AC:

6895

AN:

26078

East Asian (EAS)

AF:

0.664

AC:

26255

AN:

39552

South Asian (SAS)

AF:

0.391

AC:

33591

AN:

85944

European-Finnish (FIN)

AF:

0.236

AC:

12586

AN:

53384

Middle Eastern (MID)

AF:

0.316

AC:

1812

AN:

5728

European-Non Finnish (NFE)

AF:

0.302

AC:

335679

AN:

1110974

Other (OTH)

AF:

0.321

AC:

19385

AN:

60318

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

15606

31212

46818

62424

78030

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11242

22484

33726

44968

56210

<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:

0.327

AC:

49764

AN:

152112

Hom.:

8650

Cov.:

AF XY:

0.323

AC XY:

24007

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.374

AC:

15532

AN:

41486

American (AMR)

AF:

0.246

AC:

3756

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.268

AC:

930

AN:

3472

East Asian (EAS)

AF:

0.676

AC:

3491

AN:

5166

South Asian (SAS)

AF:

0.392

AC:

1889

AN:

4824

European-Finnish (FIN)

AF:

0.223

AC:

2369

AN:

10602

Middle Eastern (MID)

AF:

0.265

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.306

AC:

20783

AN:

67962

Other (OTH)

AF:

0.299

AC:

632

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1688

3377

5065

6754

8442

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

500

1000

1500

2000

2500

<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:

0.317

Hom.:

33039

Bravo

AF:

0.329

Asia WGS

AF:

0.460

AC:

1596

AN:

3478

EpiCase

AF:

0.307

EpiControl

AF:

0.300

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

7.3

(source)

DANN

Benign

0.69

PhyloP100

0.25

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over