16-70938692-T-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001270974.2(HYDIN):c.6917A>G(p.Glu2306Gly) variant causes a missense change. The variant allele was found at a frequency of 0.693 in 1,612,490 control chromosomes in the GnomAD database, including 402,741 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.57 ( 28289 hom., cov: 32)

Exomes 𝑓: 0.71 ( 374452 hom. )

Consequence

HYDIN
NM_001270974.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 6.29

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 made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=3.3903714E-6).

BP6

Variant 16-70938692-T-C is Benign according to our data. Variant chr16-70938692-T-C is described in ClinVar as [Benign]. Clinvar id is 402955.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-70938692-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.745 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HYDIN	NM_001270974.2 link	c.6917A>G	p.Glu2306Gly	missense_variant	Exon 44 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.6917A>G	p.Glu2306Gly	missense_variant	Exon 44 of 86	5	NM_001270974.2	ENSP00000377197.2		Q4G0P3-1
HYDIN	ENST00000309900.11 link	n.1437A>G		non_coding_transcript_exon_variant	Exon 9 of 20	1

Frequencies

GnomAD3 genomes

AF:

0.573

AC:

86938

AN:

151788

Hom.:

28284

Cov.:

show subpopulations

Gnomad AFR

AF:

0.271

Gnomad AMI

AF:

0.812

Gnomad AMR

AF:

0.504

Gnomad ASJ

AF:

0.661

Gnomad EAS

AF:

0.433

Gnomad SAS

AF:

0.505

Gnomad FIN

AF:

0.754

Gnomad MID

AF:

0.642

Gnomad NFE

AF:

0.751

Gnomad OTH

AF:

0.597

GnomAD3 exomes

AF:

0.612

AC:

152378

AN:

249038

Hom.:

50394

AF XY:

0.624

AC XY:

84279

AN XY:

135158

show subpopulations

Gnomad AFR exome

AF:

0.270

Gnomad AMR exome

AF:

0.382

Gnomad ASJ exome

AF:

0.665

Gnomad EAS exome

AF:

0.444

Gnomad SAS exome

AF:

0.506

Gnomad FIN exome

AF:

0.756

Gnomad NFE exome

AF:

0.750

Gnomad OTH exome

AF:

0.654

GnomAD4 exome

AF:

0.705

AC:

1029903

AN:

1460584

Hom.:

374452

Cov.:

AF XY:

0.701

AC XY:

509502

AN XY:

726672

show subpopulations

Gnomad4 AFR exome

AF:

0.260

Gnomad4 AMR exome

AF:

0.394

Gnomad4 ASJ exome

AF:

0.665

Gnomad4 EAS exome

AF:

0.432

Gnomad4 SAS exome

AF:

0.510

Gnomad4 FIN exome

AF:

0.759

Gnomad4 NFE exome

AF:

0.757

Gnomad4 OTH exome

AF:

0.667

GnomAD4 genome

AF:

0.573

AC:

86970

AN:

151906

Hom.:

28289

Cov.:

AF XY:

0.568

AC XY:

42182

AN XY:

74260

show subpopulations

Gnomad4 AFR

AF:

0.271

Gnomad4 AMR

AF:

0.503

Gnomad4 ASJ

AF:

0.661

Gnomad4 EAS

AF:

0.432

Gnomad4 SAS

AF:

0.506

Gnomad4 FIN

AF:

0.754

Gnomad4 NFE

AF:

0.751

Gnomad4 OTH

AF:

0.599

Alfa

AF:

0.702

Hom.:

29993

Bravo

AF:

0.542

ExAC

AF:

0.614

AC:

74225

Asia WGS

AF:

0.448

AC:

1556

AN:

3476

EpiCase

AF:

0.737

EpiControl

AF:

0.742

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jan 20, 2022

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Primary ciliary dyskinesia 5

Benign:2

Aug 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 28, 2019

Mendelics

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: Frequency -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.32

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.29

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.39

Eigen

Uncertain

0.63

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Uncertain

0.97

MetaRNN

Benign

0.0000034

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.6

PrimateAI

Uncertain

0.57

PROVEAN

Pathogenic

-5.2

REVEL

Benign

0.24

Sift

Uncertain

0.0030

Vest4

0.27

ClinPred

0.018

GERP RS

5.6

Varity_R

0.34

gMVP

0.23

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over