rs62623378

Variant names:

• chr2-195957280-A-G
• rs62623378
• NM_018897.3:c.3059T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_018897.3(DNAH7):​c.3059T>C​(p.Ile1020Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0985 in 1,563,484 control chromosomes in the GnomAD database, including 8,409 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.082 (683 hom., cov: 32)
  • Exomes 𝑓: 0.10 (7726 hom.)
• Consequence: DNAH7 NM_018897.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 2.55
• Publications: 7 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0029920936).
• BP6: Variant 2-195957280-A-G is Benign according to our data. Variant chr2-195957280-A-G is described in ClinVar as Benign. ClinVar VariationId is 377778.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH7	NM_018897.3	c.3059T>C	p.Ile1020Thr	missense_variant	Exon 19 of 65	ENST00000312428.11	NP_061720.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH7	ENST00000312428.11	c.3059T>C	p.Ile1020Thr	missense_variant	Exon 19 of 65	1	NM_018897.3	ENSP00000311273.6

Frequencies

GnomAD3 genomes AF: 0.0817 AC: 12423 AN: 152076 Hom.: 683 Cov.: 32

Gnomad AFR AF: 0.0206

Gnomad AMI AF: 0.0870

Gnomad AMR AF: 0.0871

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0843

Gnomad FIN AF: 0.125

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.0957

GnomAD2 exomes AF: 0.0899 AC: 21205 AN: 235866 AF XY: 0.0951

Gnomad AFR exome AF: 0.0165

Gnomad AMR exome AF: 0.0611

Gnomad ASJ exome AF: 0.151

Gnomad EAS exome AF: 0.000413

Gnomad FIN exome AF: 0.118

Gnomad NFE exome AF: 0.109

Gnomad OTH exome AF: 0.117

GnomAD4 exome AF: 0.100 AC: 141571 AN: 1411290 Hom.: 7726 Cov.: 31 AF XY: 0.102 AC XY: 70849 AN XY: 696516

African (AFR) AF: 0.0184 AC: 595 AN: 32406

American (AMR) AF: 0.0656 AC: 2730 AN: 41614

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 3846 AN: 25110

East Asian (EAS) AF: 0.000366 AC: 14 AN: 38212

South Asian (SAS) AF: 0.0969 AC: 7838 AN: 80866

European-Finnish (FIN) AF: 0.112 AC: 5894 AN: 52430

Middle Eastern (MID) AF: 0.181 AC: 924 AN: 5110

European-Non Finnish (NFE) AF: 0.106 AC: 113747 AN: 1077714

Other (OTH) AF: 0.103 AC: 5983 AN: 57828

GnomAD4 genome AF: 0.0816 AC: 12414 AN: 152194 Hom.: 683 Cov.: 32 AF XY: 0.0816 AC XY: 6071 AN XY: 74392

African (AFR) AF: 0.0205 AC: 853 AN: 41532

American (AMR) AF: 0.0869 AC: 1328 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.156 AC: 543 AN: 3470

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5188

South Asian (SAS) AF: 0.0844 AC: 407 AN: 4822

European-Finnish (FIN) AF: 0.125 AC: 1328 AN: 10582

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.112 AC: 7609 AN: 68000

Other (OTH) AF: 0.0947 AC: 200 AN: 2112

Alfa AF: 0.0991 Hom.: 2072

Bravo AF: 0.0742

TwinsUK AF: 0.0944 AC: 350

ALSPAC AF: 0.0929 AC: 358

ESP6500AA AF: 0.0206 AC: 77

ESP6500EA AF: 0.118 AC: 972

ExAC AF: 0.0892 AC: 10781

Asia WGS AF: 0.0330 AC: 116 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

May 13, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

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 -

DNAH7-related disorder Benign:1

Mar 11, 2024

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
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	14
DANN	Benign	0.97
DEOGEN2	Benign	0.15	T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.24
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.66	T
MetaRNN	Benign	0.0030	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		2.5
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.23
Sift	Benign	0.13	T
Polyphen		0.0050	B
Vest4		0.15
MPC		0.034
ClinPred		0.0062	T
GERP RS		4.4
Varity_R		0.14
gMVP		0.47
Mutation Taster		=97/3	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: rs62623378; hg19: chr2-196822004; COSMIC: COSV107351791;