chr2-195884788-T-C

Variant names:

• chr2-195884788-T-C
• rs62623593
• NM_018897.3:c.5560A>G

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.5560A>G​(p.Ile1854Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0352 in 1,612,554 control chromosomes in the GnomAD database, including 1,608 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 0.060 (460 hom., cov: 33)
  • Exomes 𝑓: 0.033 (1148 hom.)
• Consequence: DNAH7 NM_018897.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 2.58
• Publications: 5 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=0.0017811954).
• BP6: Variant 2-195884788-T-C is Benign according to our data. Variant chr2-195884788-T-C is described in ClinVar as Benign. ClinVar VariationId is 402750.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.14 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018897.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH7	NM_018897.3	MANE Select	c.5560A>G	p.Ile1854Val	missense	Exon 35 of 65	NP_061720.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH7	ENST00000312428.11	TSL:1 MANE Select	c.5560A>G	p.Ile1854Val	missense	Exon 35 of 65	ENSP00000311273.6

Frequencies

GnomAD3 genomes AF: 0.0594 AC: 9037 AN: 152158 Hom.: 457 Cov.: 33

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.0277

Gnomad ASJ AF: 0.0277

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.0188

Gnomad FIN AF: 0.0249

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0309

Gnomad OTH AF: 0.0488

GnomAD2 exomes AF: 0.0311 AC: 7750 AN: 248850 AF XY: 0.0295

Gnomad AFR exome AF: 0.139

Gnomad AMR exome AF: 0.0148

Gnomad ASJ exome AF: 0.0251

Gnomad EAS exome AF: 0.000334

Gnomad FIN exome AF: 0.0231

Gnomad NFE exome AF: 0.0309

Gnomad OTH exome AF: 0.0255

GnomAD4 exome AF: 0.0327 AC: 47710 AN: 1460278 Hom.: 1148 Cov.: 32 AF XY: 0.0318 AC XY: 23112 AN XY: 726326

African (AFR) AF: 0.147 AC: 4908 AN: 33422

American (AMR) AF: 0.0164 AC: 731 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.0253 AC: 660 AN: 26124

East Asian (EAS) AF: 0.000277 AC: 11 AN: 39668

South Asian (SAS) AF: 0.0223 AC: 1920 AN: 86188

European-Finnish (FIN) AF: 0.0267 AC: 1425 AN: 53336

Middle Eastern (MID) AF: 0.0160 AC: 84 AN: 5238

European-Non Finnish (NFE) AF: 0.0323 AC: 35851 AN: 1111326

Other (OTH) AF: 0.0352 AC: 2120 AN: 60290

GnomAD4 genome AF: 0.0596 AC: 9069 AN: 152276 Hom.: 460 Cov.: 33 AF XY: 0.0568 AC XY: 4229 AN XY: 74456

African (AFR) AF: 0.144 AC: 5962 AN: 41542

American (AMR) AF: 0.0276 AC: 422 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0277 AC: 96 AN: 3470

East Asian (EAS) AF: 0.000964 AC: 5 AN: 5188

South Asian (SAS) AF: 0.0189 AC: 91 AN: 4824

European-Finnish (FIN) AF: 0.0249 AC: 264 AN: 10622

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0309 AC: 2104 AN: 68016

Other (OTH) AF: 0.0540 AC: 114 AN: 2112

Alfa AF: 0.0383 Hom.: 538

Bravo AF: 0.0634

TwinsUK AF: 0.0340 AC: 126

ALSPAC AF: 0.0306 AC: 118

ESP6500AA AF: 0.130 AC: 480

ESP6500EA AF: 0.0308 AC: 252

ExAC AF: 0.0341 AC: 4118

Asia WGS AF: 0.0390 AC: 136 AN: 3478

EpiCase AF: 0.0287

EpiControl AF: 0.0301

ClinVar

Significance: Benign

Submissions summary: Benign:3

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

DNAH7-related disorder Benign:1

Jul 29, 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 v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.68	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	19
DANN	Benign	0.51
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.051
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.86	D
MetaRNN	Benign	0.0018	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.26	N
PhyloP100		2.6
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.22	N
REVEL	Benign	0.062
Sift	Benign	0.80	T
Polyphen		0.0010	B
Vest4		0.063
MPC		0.028
ClinPred		0.015	T
GERP RS		5.7
Varity_R		0.089
gMVP		0.15
Mutation Taster		=98/2	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: rs62623593; hg19: chr2-196749512;