rs116352827

Variant names:

• chr2-195756164-T-C
• rs116352827
• NM_018897.3:c.11555A>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.11555A>G​(p.Asn3852Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00306 in 1,607,940 control chromosomes in the GnomAD database, including 131 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.017 (68 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (63 hom.)
• Consequence: DNAH7 NM_018897.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0180
• Publications: 3 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), ClinGen
• male infertility with azoospermia or oligozoospermia due to single gene mutation

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

LOC107985972 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0032253861).
• BP6: Variant 2-195756164-T-C is Benign according to our data. Variant chr2-195756164-T-C is described in ClinVar as Benign. ClinVar VariationId is 709627.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0558 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH7	NM_018897.3	MANE Select	c.11555A>G	p.Asn3852Ser	missense	Exon 62 of 65	NP_061720.2	Q8WXX0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH7	ENST00000312428.11	TSL:1 MANE Select	c.11555A>G	p.Asn3852Ser	missense	Exon 62 of 65	ENSP00000311273.6	Q8WXX0-1
	DNAH7	ENST00000409063.5	TSL:1	c.1004A>G	p.Asn335Ser	missense	Exon 7 of 10	ENSP00000386912.1	Q8WXX0-2
	DNAH7	ENST00000438565.1	TSL:3	c.35A>G	p.Asn12Ser	missense	Exon 1 of 3	ENSP00000409732.1	H7C362

Frequencies

GnomAD3 genomes AF: 0.0168 AC: 2549 AN: 152176 Hom.: 69 Cov.: 32

Gnomad AFR AF: 0.0578

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00752

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.0124

GnomAD2 exomes AF: 0.00427 AC: 1053 AN: 246356 AF XY: 0.00344

Gnomad AFR exome AF: 0.0587

Gnomad AMR exome AF: 0.00314

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000233

Gnomad NFE exome AF: 0.000134

Gnomad OTH exome AF: 0.00285

GnomAD4 exome AF: 0.00163 AC: 2368 AN: 1455646 Hom.: 63 Cov.: 31 AF XY: 0.00139 AC XY: 1009 AN XY: 723336

African (AFR) AF: 0.0569 AC: 1895 AN: 33280

American (AMR) AF: 0.00336 AC: 148 AN: 44034

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25978

East Asian (EAS) AF: 0.00 AC: 0 AN: 39548

South Asian (SAS) AF: 0.000176 AC: 15 AN: 85402

European-Finnish (FIN) AF: 0.000394 AC: 21 AN: 53332

Middle Eastern (MID) AF: 0.00226 AC: 13 AN: 5744

European-Non Finnish (NFE) AF: 0.0000460 AC: 51 AN: 1108140

Other (OTH) AF: 0.00374 AC: 225 AN: 60188

GnomAD4 genome AF: 0.0168 AC: 2553 AN: 152294 Hom.: 68 Cov.: 32 AF XY: 0.0167 AC XY: 1244 AN XY: 74474

African (AFR) AF: 0.0577 AC: 2397 AN: 41554

American (AMR) AF: 0.00751 AC: 115 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.000283 AC: 3 AN: 10618

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68022

Other (OTH) AF: 0.0123 AC: 26 AN: 2112

Alfa AF: 0.00602 Hom.: 62

Bravo AF: 0.0184

ESP6500AA AF: 0.0567 AC: 208

ESP6500EA AF: 0.000122 AC: 1

ExAC AF: 0.00537 AC: 649

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.74	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	21
DANN	Benign	0.79
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.11
FATHMM_MKL	Benign	0.75	D
LIST_S2	Uncertain	0.90	D
MetaRNN	Benign	0.0032	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.64	N
PhyloP100		0.018
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.12
Sift	Benign	0.75	T
Sift4G	Benign	0.48	T
Polyphen		0.020	B
Vest4		0.13
MVP		0.14
MPC		0.030
ClinPred		0.018	T
GERP RS		5.2
PromoterAI		0.011	Neutral
Varity_R		0.14
gMVP		0.25
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: rs116352827; hg19: chr2-196620888;