Variant 16-70921012-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 13/18 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 made for transcript

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
HYDIN	NM_001270974.2 link	c.7364C>A	p.Pro2455Gln	missense_variant	46/86	ENST00000393567.7	NP_001257903.1	Q4G0P3-1

Ensembl

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

GnomAD3 exomes

AF:

0.997

AC:

199260

AN:

199800

Hom.:

99526

AF XY:

0.997

AC XY:

107830

AN XY:

108114

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 SAS 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

Gnomad4 AFR exome

AF:

1.00

Gnomad4 AMR exome

AF:

0.999

Gnomad4 ASJ exome

AF:

1.00

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.999

Gnomad4 FIN exome

AF:

0.999

Gnomad4 NFE exome

AF:

0.996

Gnomad4 OTH exome

AF:

0.998

GnomAD4 genome

AF:

0.998

AC:

150939

AN:

151308

Hom.:

75286

Cov.:

AF XY:

0.998

AC XY:

73672

AN XY:

73830

show subpopulations

Gnomad4 AFR

AF:

0.999

Gnomad4 AMR

AF:

0.998

Gnomad4 ASJ

AF:

0.999

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

0.999

Gnomad4 FIN

AF:

0.999

Gnomad4 NFE

AF:

0.996

Gnomad4 OTH

AF:

0.998

Alfa

AF:

0.996

Hom.:

61781

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 20, 2021	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

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

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

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

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

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

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