16-70921012-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001270974.2(HYDIN):c.7364C>A(p.Pro2455Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.998 in 151,308 control chromosomes in the GnomAD database, including 75,286 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 1.0 ( 75286 hom., cov: 24)

Exomes 𝑓: 1.0 ( 707428 hom. )

Failed GnomAD Quality Control

Consequence

HYDIN
NM_001270974.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 2.45

Variant links:

Genes affected

HYDIN (HGNC:19368): (HYDIN axonemal central pair apparatus protein) This gene encodes a protein that may be involved in cilia motility. Mutations in this gene cause of autosomal recessive primary ciliary dyskinesia-5, a disorder characterized by the accumulation of cerebrospinal fluid within the ventricles of the brain. A duplicate copy of this gene has been found in humans on chromosome 1. [provided by RefSeq, Jan 2013]

HYDIN links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=5.8863645E-7).

BP6

Variant 16-70921012-G-T is Benign according to our data. Variant chr16-70921012-G-T is described in ClinVar as [Benign]. Clinvar id is 402954.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-70921012-G-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.991 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HYDIN	NM_001270974.2 link	c.7364C>A	p.Pro2455Gln	missense_variant	Exon 46 of 86	ENST00000393567.7	NP_001257903.1	Q4G0P3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HYDIN	ENST00000393567.7 link	c.7364C>A	p.Pro2455Gln	missense_variant	Exon 46 of 86	5	NM_001270974.2	ENSP00000377197.2		Q4G0P3-1
HYDIN	ENST00000309900.11 link	n.2036C>A		non_coding_transcript_exon_variant	Exon 12 of 20	1

Frequencies

GnomAD3 genomes

AF:

0.998

AC:

150821

AN:

151190

Hom.:

75227

Cov.:

show subpopulations

Gnomad AFR

AF:

0.999

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.998

Gnomad ASJ

AF:

0.999

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.999

Gnomad FIN

AF:

0.999

Gnomad MID

AF:

1.00

Gnomad NFE

AF:

0.996

Gnomad OTH

AF:

0.998

GnomAD2 exomes

AF:

0.997

AC:

199260

AN:

199800

AF XY:

0.997

show subpopulations

Gnomad AFR exome

AF:

0.999

Gnomad AMR exome

AF:

0.999

Gnomad ASJ exome

AF:

1.00

Gnomad EAS exome

AF:

1.00

Gnomad FIN exome

AF:

0.999

Gnomad NFE exome

AF:

0.995

Gnomad OTH exome

AF:

0.996

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.997

AC:

1418969

AN:

1423256

Hom.:

707428

Cov.:

AF XY:

0.997

AC XY:

705764

AN XY:

707820

show subpopulations

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

African (AFR)

AF:

1.00

AC:

32078

AN:

32094

American (AMR)

AF:

0.999

AC:

40269

AN:

40310

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

24446

AN:

24452

East Asian (EAS)

AF:

1.00

AC:

39542

AN:

39542

South Asian (SAS)

AF:

0.999

AC:

81175

AN:

81268

European-Finnish (FIN)

AF:

0.999

AC:

52012

AN:

52082

Middle Eastern (MID)

AF:

1.00

AC:

5570

AN:

5572

European-Non Finnish (NFE)

AF:

0.996

AC:

1085178

AN:

1089112

Other (OTH)

AF:

0.998

AC:

58699

AN:

58824

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.334

Heterozygous variant carriers

245

489

734

978

1223

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.998

AC:

150939

AN:

151308

Hom.:

75286

Cov.:

AF XY:

0.998

AC XY:

73672

AN XY:

73830

show subpopulations

African (AFR)

AF:

0.999

AC:

41133

AN:

41170

American (AMR)

AF:

0.998

AC:

15167

AN:

15202

Ashkenazi Jewish (ASJ)

AF:

0.999

AC:

3468

AN:

3470

East Asian (EAS)

AF:

1.00

AC:

5140

AN:

5140

South Asian (SAS)

AF:

0.999

AC:

4694

AN:

4698

European-Finnish (FIN)

AF:

0.999

AC:

10502

AN:

10512

Middle Eastern (MID)

AF:

1.00

AC:

294

AN:

294

European-Non Finnish (NFE)

AF:

0.996

AC:

67556

AN:

67832

Other (OTH)

AF:

0.998

AC:

2075

AN:

2080

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.431

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.996

Hom.:

106391

Bravo

AF:

0.997

ESP6500AA

AF:

0.999

AC:

3580

ESP6500EA

AF:

0.991

AC:

7999

ExAC

AF:

0.993

AC:

119175

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

May 20, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Mar 28, 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: MAF -

Primary ciliary dyskinesia 5

Benign:1

Aug 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.050

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.72

CADD

Benign

(source)

DANN

Benign

0.24

DEOGEN2

Benign

0.019

Eigen

Benign

-0.94

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.064

MetaRNN

Benign

5.9e-7

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-2.4

PhyloP100

2.4

PrimateAI

Benign

0.34

PROVEAN

Benign

2.6

REVEL

Benign

0.20

Sift

Benign

1.0

Vest4

0.038

ClinPred

0.011

GERP RS

5.9

Varity_R

0.024

gMVP

0.047

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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16-70921012-G-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over