dbSNP rs115124743: DNAH7:p.Val873Val (chr2-195960532-G-C) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_018897.3(DNAH7):c.2619C>G(p.Val873Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0341 in 1,614,102 control chromosomes in the GnomAD database, including 1,005 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.030 ( 85 hom., cov: 32)

Exomes 𝑓: 0.034 ( 920 hom. )

Consequence

DNAH7
NM_018897.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0290

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 2-195960532-G-C is Benign according to our data. Variant chr2-195960532-G-C is described in ClinVar as [Benign]. Clinvar id is 402754.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.029 with no splicing effect.

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0609 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH7	NM_018897.3 link	c.2619C>G	p.Val873Val	synonymous_variant	Exon 18 of 65	ENST00000312428.11	NP_061720.2	Q8WXX0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH7	ENST00000312428.11 link	c.2619C>G	p.Val873Val	synonymous_variant	Exon 18 of 65	1	NM_018897.3	ENSP00000311273.6		Q8WXX0-1

Frequencies

GnomAD3 genomes

AF:

0.0302

AC:

4588

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00934

Gnomad AMI

AF:

0.0537

Gnomad AMR

AF:

0.0380

Gnomad ASJ

AF:

0.0328

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0135

Gnomad FIN

AF:

0.0497

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.0408

Gnomad OTH

AF:

0.0321

GnomAD3 exomes

AF:

0.0291

AC:

7260

AN:

249194

Hom.:

149

AF XY:

0.0305

AC XY:

4129

AN XY:

135174

show subpopulations

Gnomad AFR exome

AF:

0.00756

Gnomad AMR exome

AF:

0.0248

Gnomad ASJ exome

AF:

0.0292

Gnomad EAS exome

AF:

0.000167

Gnomad SAS exome

AF:

0.0142

Gnomad FIN exome

AF:

0.0399

Gnomad NFE exome

AF:

0.0395

Gnomad OTH exome

AF:

0.0385

GnomAD4 exome

AF:

0.0345

AC:

50383

AN:

1461868

Hom.:

920

Cov.:

AF XY:

0.0344

AC XY:

25047

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.00762

Gnomad4 AMR exome

AF:

0.0268

Gnomad4 ASJ exome

AF:

0.0277

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0148

Gnomad4 FIN exome

AF:

0.0373

Gnomad4 NFE exome

AF:

0.0382

Gnomad4 OTH exome

AF:

0.0344

GnomAD4 genome

AF:

0.0301

AC:

4587

AN:

152234

Hom.:

Cov.:

AF XY:

0.0305

AC XY:

2271

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.00929

Gnomad4 AMR

AF:

0.0379

Gnomad4 ASJ

AF:

0.0328

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0139

Gnomad4 FIN

AF:

0.0497

Gnomad4 NFE

AF:

0.0408

Gnomad4 OTH

AF:

0.0318

Alfa

AF:

0.0361

Hom.:

Bravo

AF:

0.0280

Asia WGS

AF:

0.00635

AC:

AN:

3478

EpiCase

AF:

0.0463

EpiControl

AF:

0.0460

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 29, 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 -

DNAH7-related disorder

Benign:1

Oct 17, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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). -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

3.1

DANN

Benign

0.54

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