rs75859635

chr2-195873641-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_018897.3(DNAH7):c.6340A>G(p.Thr2114Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0368 in 1,531,804 control chromosomes in the GnomAD database, including 1,169 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.031 (94 hom., cov: 32)
  • Exomes 𝑓: 0.037 (1075 hom.)
• Consequence: DNAH7 NM_018897.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.91

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.007309526).
• BP6: Variant 2-195873641-T-C is Benign according to our data. Variant chr2-195873641-T-C is described in ClinVar as [Benign]. Clinvar id is 402749.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-195873641-T-C is described in Lovd as [Benign].
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0591 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH7	NM_018897.3	c.6340A>G	p.Thr2114Ala	missense_variant	39/65	ENST00000312428.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH7	ENST00000312428.11	c.6340A>G	p.Thr2114Ala	missense_variant	39/65	1	NM_018897.3	P1

Frequencies

GnomAD3 genomes AF: 0.0312 AC: 4751 AN: 152086 Hom.: 94 Cov.: 32

Gnomad AFR AF: 0.0168

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.0300

Gnomad ASJ AF: 0.0294

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0108

Gnomad FIN AF: 0.0365

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0427

Gnomad OTH AF: 0.0346

GnomAD3 exomes AF: 0.0303 AC: 5804 AN: 191358 Hom.: 126 AF XY: 0.0317 AC XY: 3342 AN XY: 105542

Gnomad AFR exome AF: 0.0158

Gnomad AMR exome AF: 0.0178

Gnomad ASJ exome AF: 0.0321

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0158

Gnomad FIN exome AF: 0.0339

Gnomad NFE exome AF: 0.0407

Gnomad OTH exome AF: 0.0319

GnomAD4 exome AF: 0.0374 AC: 51645 AN: 1379600 Hom.: 1075 Cov.: 28 AF XY: 0.0370 AC XY: 25347 AN XY: 685046

Gnomad4 AFR exome AF: 0.0168

Gnomad4 AMR exome AF: 0.0202

Gnomad4 ASJ exome AF: 0.0316

Gnomad4 EAS exome AF: 0.0000560

Gnomad4 SAS exome AF: 0.0161

Gnomad4 FIN exome AF: 0.0354

Gnomad4 NFE exome AF: 0.0413

Gnomad4 OTH exome AF: 0.0355

GnomAD4 genome AF: 0.0312 AC: 4750 AN: 152204 Hom.: 94 Cov.: 32 AF XY: 0.0304 AC XY: 2263 AN XY: 74420

Gnomad4 AFR AF: 0.0167

Gnomad4 AMR AF: 0.0300

Gnomad4 ASJ AF: 0.0294

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0108

Gnomad4 FIN AF: 0.0365

Gnomad4 NFE AF: 0.0427

Gnomad4 OTH AF: 0.0343

Alfa AF: 0.0401 Hom.: 205

Bravo AF: 0.0311

TwinsUK AF: 0.0399 AC: 148

ALSPAC AF: 0.0413 AC: 159

ESP6500AA AF: 0.0144 AC: 52

ESP6500EA AF: 0.0434 AC: 353

ExAC AF: 0.0307 AC: 3712

Asia WGS AF: 0.00780 AC: 27 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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: Frequency -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.49
Cadd	Benign	21
Dann	Benign	0.97
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.022
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.85	D
MetaRNN	Benign	0.0073	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.81	L
MutationTaster	Benign	1.0	D
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.13
Sift	Benign	0.41	T
Polyphen		0.019	B
Vest4		0.29
MPC		0.035
ClinPred		0.0069	T
GERP RS		4.8
Varity_R		0.35
gMVP		0.50

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: rs75859635; hg19: chr2-196738365;