rs115124743

chr2-195960532-G-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_018897.3(DNAH7):c.2619C>G(p.Val873=) 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0290

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]

ACMG classification

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/exons	MANE	UniProt
DNAH7	NM_018897.3	c.2619C>G	p.Val873=	synonymous_variant	18/65	ENST00000312428.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH7	ENST00000312428.11	c.2619C>G	p.Val873=	synonymous_variant	18/65	1	NM_018897.3	P1

Frequencies

GnomAD3 genomes AF: 0.0302 AC: 4588 AN: 152116 Hom.: 85 Cov.: 32

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

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.: 31 AF XY: 0.0344 AC XY: 25047 AN XY: 727236

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.: 85 Cov.: 32 AF XY: 0.0305 AC XY: 2271 AN XY: 74444

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.: 34

Bravo AF: 0.0280

Asia WGS AF: 0.00635 AC: 22 AN: 3478

EpiCase AF: 0.0463

EpiControl AF: 0.0460

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 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 -

DNAH7-related condition Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 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
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

Other links and lift over

dbSNP: rs115124743; hg19: chr2-196825256;