2-195926552-T-G

Variant names:

• chr2-195926552-T-G
• rs1489802
• NM_018897.3:c.3486A>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_018897.3(DNAH7):​c.3486A>C​(p.Ala1162Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.618 in 1,591,136 control chromosomes in the GnomAD database, including 314,517 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.50 (22192 hom., cov: 31)
  • Exomes 𝑓: 0.63 (292325 hom.)
• Consequence: DNAH7 NM_018897.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.184
• Publications: 26 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 2-195926552-T-G is Benign according to our data. Variant chr2-195926552-T-G is described in ClinVar as Benign. ClinVar VariationId is 402753.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.184 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.639 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH7	NM_018897.3	c.3486A>C	p.Ala1162Ala	synonymous_variant	Exon 22 of 65	ENST00000312428.11	NP_061720.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH7	ENST00000312428.11	c.3486A>C	p.Ala1162Ala	synonymous_variant	Exon 22 of 65	1	NM_018897.3	ENSP00000311273.6

Frequencies

GnomAD3 genomes AF: 0.499 AC: 75818 AN: 151808 Hom.: 22189 Cov.: 31

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.572

Gnomad AMR AF: 0.540

Gnomad ASJ AF: 0.520

Gnomad EAS AF: 0.574

Gnomad SAS AF: 0.652

Gnomad FIN AF: 0.656

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.644

Gnomad OTH AF: 0.501

GnomAD2 exomes AF: 0.597 AC: 137100 AN: 229746 AF XY: 0.605

Gnomad AFR exome AF: 0.164

Gnomad AMR exome AF: 0.586

Gnomad ASJ exome AF: 0.528

Gnomad EAS exome AF: 0.562

Gnomad FIN exome AF: 0.663

Gnomad NFE exome AF: 0.644

Gnomad OTH exome AF: 0.588

GnomAD4 exome AF: 0.631 AC: 908071 AN: 1439210 Hom.: 292325 Cov.: 38 AF XY: 0.632 AC XY: 452432 AN XY: 715978

African (AFR) AF: 0.151 AC: 4877 AN: 32266

American (AMR) AF: 0.582 AC: 23499 AN: 40386

Ashkenazi Jewish (ASJ) AF: 0.528 AC: 13472 AN: 25510

East Asian (EAS) AF: 0.614 AC: 23440 AN: 38192

South Asian (SAS) AF: 0.640 AC: 52689 AN: 82324

European-Finnish (FIN) AF: 0.660 AC: 35025 AN: 53028

Middle Eastern (MID) AF: 0.450 AC: 2558 AN: 5682

European-Non Finnish (NFE) AF: 0.651 AC: 717530 AN: 1102456

Other (OTH) AF: 0.589 AC: 34981 AN: 59366

GnomAD4 genome AF: 0.499 AC: 75827 AN: 151926 Hom.: 22192 Cov.: 31 AF XY: 0.502 AC XY: 37289 AN XY: 74244

African (AFR) AF: 0.176 AC: 7298 AN: 41454

American (AMR) AF: 0.541 AC: 8245 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.520 AC: 1801 AN: 3464

East Asian (EAS) AF: 0.573 AC: 2963 AN: 5168

South Asian (SAS) AF: 0.653 AC: 3138 AN: 4808

European-Finnish (FIN) AF: 0.656 AC: 6914 AN: 10538

Middle Eastern (MID) AF: 0.469 AC: 137 AN: 292

European-Non Finnish (NFE) AF: 0.644 AC: 43757 AN: 67930

Other (OTH) AF: 0.499 AC: 1052 AN: 2108

Alfa AF: 0.602 Hom.: 121458

Bravo AF: 0.472

Asia WGS AF: 0.566 AC: 1965 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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: Frequency -

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	-0.83
CADD	Benign	0.41
DANN	Benign	0.30
PhyloP100		-0.18
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: rs1489802; hg19: chr2-196791276; COSMIC: COSV56765630;