11-6498285-C-A

Position:

chr11-6498285-C-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 1P and 7B. PP2BP4_StrongBP6_ModerateBS2_Supporting

The NM_144666.3(DNHD1):c.70C>A(p.His24Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00012 in 1,614,220 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000098 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00012 ( 3 hom. )

Consequence

DNHD1
NM_144666.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.0880

Variant links:

Genes affected

DNHD1 (HGNC:26532): (dynein heavy chain domain 1) Predicted to enable dynein intermediate chain binding activity; dynein light intermediate chain binding activity; and minus-end-directed microtubule motor activity. Predicted to be involved in cilium movement. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

DNHD1 links:

DNHD1 (HGNC:):

DNHD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), DNHD1. . Gene score misZ 3.4791 (greater than the threshold 3.09). Trascript score misZ 3.2933 (greater than threshold 3.09). GenCC has associacion of gene with spermatogenic failure 65.

BP4

Computational evidence support a benign effect (MetaRNN=0.0043008924).

BP6

Variant 11-6498285-C-A is Benign according to our data. Variant chr11-6498285-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 782867.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 3 AR geneVariant has number of homozygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNHD1	NM_144666.3 linkuse as main transcript	c.70C>A	p.His24Asn	missense_variant	3/43	ENST00000254579.11	NP_653267.2	Q96M86-3B0I1S4
DNHD1	NM_173589.4 linkuse as main transcript	c.70C>A	p.His24Asn	missense_variant	2/8		NP_775860.3	Q96M86-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNHD1	ENST00000254579.11 linkuse as main transcript	c.70C>A	p.His24Asn	missense_variant	3/43	5	NM_144666.3	ENSP00000254579.6		Q96M86-3
ENSG00000283977	ENST00000640959.1 linkuse as main transcript	n.*313C>A		downstream_gene_variant		4		ENSP00000491841.1

Frequencies

GnomAD3 genomes

AF:

0.0000985

AC:

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00212

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000286

AC:

AN:

251322

Hom.:

AF XY:

0.000162

AC XY:

AN XY:

135832

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00364

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000652

GnomAD4 exome

AF:

0.000122

AC:

178

AN:

1461884

Hom.:

Cov.:

AF XY:

0.0000825

AC XY:

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00204

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00154

GnomAD4 genome

AF:

0.0000985

AC:

AN:

152336

Hom.:

Cov.:

AF XY:

0.0000805

AC XY:

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00212

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000290

Hom.:

Bravo

AF:

0.000261

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.000239

AC:

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

DNHD1-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 31, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.97

DANN

Benign

0.71

DEOGEN2

Benign

0.0068

T;.;T

Eigen

Benign

-0.95

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.088

LIST_S2

Benign

0.30

T;T;.

M_CAP

Benign

0.0033

MetaRNN

Benign

0.0043

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.46

N;N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.54

N;N;N

REVEL

Benign

0.016

Sift

Benign

0.36

T;T;T

Sift4G

Uncertain

0.015

D;T;D

Polyphen

0.0

B;B;B

Vest4

0.092

MVP

0.31

MPC

0.13

ClinPred

0.013

GERP RS

2.5

Varity_R

0.046

gMVP

0.031

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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