Genetic Variant NM_213607.3:c.52G>T (chr17-44901050-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_213607.3(DNAAF19):c.52G>T(p.Ala18Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000069 in 1,448,542 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A18T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

DNAAF19
NM_213607.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.28

Publications

0 publications found

Variant links:

Genes affected

DNAAF19 (HGNC:32700): (coiled-coil domain containing 103) Enables protein homodimerization activity. Involved in axonemal dynein complex assembly; cilium movement; and determination of left/right symmetry. Predicted to be located in axoneme. Predicted to be part of outer dynein arm. Implicated in primary ciliary dyskinesia 17. [provided by Alliance of Genome Resources, Apr 2022]

DNAAF19 Gene-Disease associations (from GenCC):

primary ciliary dyskinesia 17
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: ClinGen, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
primary ciliary dyskinesia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

DNAAF19 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12506402).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_213607.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DNAAF19	NM_213607.3	MANE Select	c.52G>T	p.Ala18Ser	missense	Exon 2 of 4	NP_998772.1	Q8IW40-1
DNAAF19	NM_001258395.2		c.52G>T	p.Ala18Ser	missense	Exon 2 of 4	NP_001245324.1	Q8IW40-1
DNAAF19	NM_001258396.2		c.52G>T	p.Ala18Ser	missense	Exon 2 of 4	NP_001245325.1	Q8IW40-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DNAAF19	ENST00000417826.3	TSL:1 MANE Select	c.52G>T	p.Ala18Ser	missense	Exon 2 of 4	ENSP00000391692.2	Q8IW40-1
DNAAF19	ENST00000410006.6	TSL:2	c.52G>T	p.Ala18Ser	missense	Exon 2 of 4	ENSP00000387252.1	Q8IW40-1
DNAAF19	ENST00000357776.6	TSL:2	c.52G>T	p.Ala18Ser	missense	Exon 2 of 4	ENSP00000350420.2	F8W6J8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.90e-7

AC:

AN:

1448542

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

720794

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32486

American (AMR)

AF:

0.00

AC:

AN:

39840

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25604

East Asian (EAS)

AF:

0.00

AC:

AN:

39290

South Asian (SAS)

AF:

0.00

AC:

AN:

83502

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53358

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5736

European-Non Finnish (NFE)

AF:

9.02e-7

AC:

AN:

1108880

Other (OTH)

AF:

0.00

AC:

AN:

59846

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.057

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.032

Eigen

Benign

0.094

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.79

M_CAP

Benign

0.015

MetaRNN

Benign

0.13

MetaSVM

Benign

-0.60

MutationAssessor

Benign

1.6

PhyloP100

4.3

PrimateAI

Benign

0.37

PROVEAN

Benign

0.43

REVEL

Benign

0.20

Sift

Benign

0.36

Sift4G

Benign

0.39

Polyphen

0.39

Vest4

0.18

MutPred

0.19

Gain of phosphorylation at A18 (P = 0.0579)

MVP

0.66

MPC

0.41

ClinPred

0.47

GERP RS

5.8

Varity_R

0.065

gMVP

0.13

Mutation Taster

=86/14

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over