rs6434811

Variant names:

• chr2-196001696-C-T
• rs6434811
• NM_018897.3:c.1152G>A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_018897.3(DNAH7):​c.1152G>A​(p.Thr384Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.87 in 1,577,548 control chromosomes in the GnomAD database, including 612,613 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.72 (44685 hom., cov: 32)
  • Exomes 𝑓: 0.89 (567928 hom.)
• Consequence: DNAH7 NM_018897.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0560
• Publications: 19 publications found

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 Gene-Disease associations (from GenCC):

• ciliary dyskinesia, primary, 50

  Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
• male infertility with azoospermia or oligozoospermia due to single gene mutation

  Inheritance: AR Classification: LIMITED Submitted by: King Faisal Specialist Hospital and Research Center

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BP6: Variant 2-196001696-C-T is Benign according to our data. Variant chr2-196001696-C-T is described in ClinVar as Benign. ClinVar VariationId is 402756.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.056 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.903 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH7	NM_018897.3	c.1152G>A	p.Thr384Thr	synonymous_variant	Exon 11 of 65	ENST00000312428.11	NP_061720.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH7	ENST00000312428.11	c.1152G>A	p.Thr384Thr	synonymous_variant	Exon 11 of 65	1	NM_018897.3	ENSP00000311273.6
DNAH7	ENST00000410072.5	c.1152G>A	p.Thr384Thr	synonymous_variant	Exon 11 of 13	2		ENSP00000386260.1

Frequencies

GnomAD3 genomes AF: 0.721 AC: 109593 AN: 151970 Hom.: 44694 Cov.: 32

Gnomad AFR AF: 0.310

Gnomad AMI AF: 0.924

Gnomad AMR AF: 0.772

Gnomad ASJ AF: 0.885

Gnomad EAS AF: 0.662

Gnomad SAS AF: 0.924

Gnomad FIN AF: 0.898

Gnomad MID AF: 0.886

Gnomad NFE AF: 0.909

Gnomad OTH AF: 0.752

GnomAD2 exomes AF: 0.834 AC: 191598 AN: 229846 AF XY: 0.850

Gnomad AFR exome AF: 0.294

Gnomad AMR exome AF: 0.778

Gnomad ASJ exome AF: 0.887

Gnomad EAS exome AF: 0.657

Gnomad FIN exome AF: 0.902

Gnomad NFE exome AF: 0.910

Gnomad OTH exome AF: 0.862

GnomAD4 exome AF: 0.886 AC: 1263540 AN: 1425460 Hom.: 567928 Cov.: 44 AF XY: 0.890 AC XY: 627723 AN XY: 705622

African (AFR) AF: 0.282 AC: 9036 AN: 32000

American (AMR) AF: 0.785 AC: 30835 AN: 39302

Ashkenazi Jewish (ASJ) AF: 0.891 AC: 22285 AN: 25018

East Asian (EAS) AF: 0.692 AC: 26740 AN: 38660

South Asian (SAS) AF: 0.922 AC: 72730 AN: 78900

European-Finnish (FIN) AF: 0.897 AC: 47461 AN: 52940

Middle Eastern (MID) AF: 0.869 AC: 4881 AN: 5620

European-Non Finnish (NFE) AF: 0.914 AC: 999603 AN: 1094196

Other (OTH) AF: 0.849 AC: 49969 AN: 58824

GnomAD4 genome AF: 0.721 AC: 109588 AN: 152088 Hom.: 44685 Cov.: 32 AF XY: 0.724 AC XY: 53853 AN XY: 74366

African (AFR) AF: 0.309 AC: 12809 AN: 41394

American (AMR) AF: 0.772 AC: 11795 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.885 AC: 3074 AN: 3472

East Asian (EAS) AF: 0.662 AC: 3426 AN: 5178

South Asian (SAS) AF: 0.924 AC: 4458 AN: 4824

European-Finnish (FIN) AF: 0.898 AC: 9524 AN: 10600

Middle Eastern (MID) AF: 0.888 AC: 261 AN: 294

European-Non Finnish (NFE) AF: 0.909 AC: 61819 AN: 68020

Other (OTH) AF: 0.747 AC: 1579 AN: 2114

Alfa AF: 0.848 Hom.: 179695

Bravo AF: 0.690

Asia WGS AF: 0.749 AC: 2606 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Sep 11, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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: Frequency -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	0.87
DANN	Benign	0.61
PhyloP100		0.056
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6434811; hg19: chr2-196866420; COSMIC: COSV56767272;