Variant 2-195754381-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_018897.3(DNAH7):c.11720A>G(p.Tyr3907Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00686 in 1,614,006 control chromosomes in the GnomAD database, including 57 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0048 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0071 ( 56 hom. )

Consequence

DNAH7
NM_018897.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 3.41

Variant links:

Genes affected

DNAH7 (HGNC:18661): (dynein axonemal heavy chain 7) DNAH7 is a component of the inner dynein arm of ciliary axonemes (Zhang et al., 2002 [PubMed 11877439]).[supplied by OMIM, Mar 2008]

DNAH7 links:

LOC107985972 (HGNC:):

LOC107985972 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01423794).

BP6

Variant 2-195754381-T-C is Benign according to our data. Variant chr2-195754381-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 718311.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 56 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH7	NM_018897.3 linkuse as main transcript	c.11720A>G	p.Tyr3907Cys	missense_variant	63/65	ENST00000312428.11
LOC107985972	XR_001739837.2 linkuse as main transcript	n.1828-3719T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH7	ENST00000312428.11 linkuse as main transcript	c.11720A>G	p.Tyr3907Cys	missense_variant	63/65	1	NM_018897.3	P1	Q8WXX0-1
DNAH7	ENST00000409063.5 linkuse as main transcript	c.1169A>G	p.Tyr390Cys	missense_variant	8/10	1			Q8WXX0-2
DNAH7	ENST00000438565.1 linkuse as main transcript	c.66+1752A>G		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00483

AC:

735

AN:

152110

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00181

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00518

Gnomad ASJ

AF:

0.00461

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.000753

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00797

Gnomad OTH

AF:

0.00480

GnomAD3 exomes

AF:

0.00457

AC:

1139

AN:

249328

Hom.:

AF XY:

0.00472

AC XY:

638

AN XY:

135280

show subpopulations

Gnomad AFR exome

AF:

0.00116

Gnomad AMR exome

AF:

0.00345

Gnomad ASJ exome

AF:

0.00596

Gnomad EAS exome

AF:

0.000111

Gnomad SAS exome

AF:

0.00124

Gnomad FIN exome

AF:

0.000464

Gnomad NFE exome

AF:

0.00768

Gnomad OTH exome

AF:

0.00380

GnomAD4 exome

AF:

0.00708

AC:

10345

AN:

1461778

Hom.:

Cov.:

AF XY:

0.00701

AC XY:

5100

AN XY:

727192

show subpopulations

Gnomad4 AFR exome

AF:

0.000926

Gnomad4 AMR exome

AF:

0.00347

Gnomad4 ASJ exome

AF:

0.00559

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00121

Gnomad4 FIN exome

AF:

0.000842

Gnomad4 NFE exome

AF:

0.00856

Gnomad4 OTH exome

AF:

0.00543

GnomAD4 genome

AF:

0.00483

AC:

735

AN:

152228

Hom.:

Cov.:

AF XY:

0.00455

AC XY:

339

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.00181

Gnomad4 AMR

AF:

0.00517

Gnomad4 ASJ

AF:

0.00461

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.000753

Gnomad4 NFE

AF:

0.00797

Gnomad4 OTH

AF:

0.00475

Alfa

AF:

0.00782

Hom.:

Bravo

AF:

0.00506

TwinsUK

AF:

0.00944

AC:

ALSPAC

AF:

0.00571

AC:

ESP6500AA

AF:

0.00104

AC:

ESP6500EA

AF:

0.00836

AC:

ExAC

AF:

0.00465

AC:

562

EpiCase

AF:

0.00867

EpiControl

AF:

0.00670

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jun 01, 2024	DNAH7: BS2 -
Likely benign, criteria provided, single submitter	clinical testing	Invitae	Dec 31, 2019	- -

DNAH7-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 13, 2019

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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.29

CADD

Uncertain

DANN

Uncertain

1.0

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.60

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.96

D;D

M_CAP

Benign

0.011

MetaRNN

Benign

0.014

T;T

MetaSVM

Benign

-1.2

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.67

PROVEAN

Pathogenic

-6.8

D;D

REVEL

Benign

0.15

Sift

Uncertain

0.0010

D;D

Sift4G

Uncertain

0.019

D;.

Polyphen

1.0

.;D

Vest4

0.69

MVP

0.50

MPC

0.24

ClinPred

0.052

GERP RS

5.5

Varity_R

0.57

gMVP

0.74

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

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