2-195808809-A-G

Variant names:

• chr2-195808809-A-G
• rs13411834
• NM_018897.3:c.9956T>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.9956T>C​(p.Leu3319Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.994 in 1,613,984 control chromosomes in the GnomAD database, including 797,285 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.97 (71268 hom., cov: 32)
  • Exomes 𝑓: 1.0 (726017 hom.)
• Consequence: DNAH7 NM_018897.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 7.58
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=6.7730775E-7).
• BP6: Variant 2-195808809-A-G is Benign according to our data. Variant chr2-195808809-A-G is described in ClinVar as Benign. ClinVar VariationId is 402748.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 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.9956T>C	p.Leu3319Pro	missense	Exon 53 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.9956T>C	p.Leu3319Pro	missense	Exon 53 of 65	ENSP00000311273.6

Frequencies

GnomAD3 genomes AF: 0.966 AC: 147013 AN: 152160 Hom.: 71225 Cov.: 32

Gnomad AFR AF: 0.882

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.986

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.997

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.978

GnomAD2 exomes AF: 0.991 AC: 247140 AN: 249300 AF XY: 0.993

Gnomad AFR exome AF: 0.878

Gnomad AMR exome AF: 0.994

Gnomad ASJ exome AF: 1.00

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 1.00

Gnomad OTH exome AF: 0.997

GnomAD4 exome AF: 0.997 AC: 1456599 AN: 1461706 Hom.: 726017 Cov.: 54 AF XY: 0.997 AC XY: 724902 AN XY: 727146

African (AFR) AF: 0.879 AC: 29425 AN: 33470

American (AMR) AF: 0.993 AC: 44404 AN: 44706

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 26132 AN: 26132

East Asian (EAS) AF: 1.00 AC: 39670 AN: 39670

South Asian (SAS) AF: 1.00 AC: 86225 AN: 86252

European-Finnish (FIN) AF: 1.00 AC: 53402 AN: 53402

Middle Eastern (MID) AF: 0.993 AC: 5725 AN: 5766

European-Non Finnish (NFE) AF: 1.00 AC: 1111718 AN: 1111920

Other (OTH) AF: 0.992 AC: 59898 AN: 60388

GnomAD4 genome AF: 0.966 AC: 147115 AN: 152278 Hom.: 71268 Cov.: 32 AF XY: 0.967 AC XY: 72021 AN XY: 74452

African (AFR) AF: 0.882 AC: 36645 AN: 41528

American (AMR) AF: 0.986 AC: 15097 AN: 15306

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3472 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5174 AN: 5174

South Asian (SAS) AF: 1.00 AC: 4824 AN: 4826

European-Finnish (FIN) AF: 1.00 AC: 10618 AN: 10618

Middle Eastern (MID) AF: 0.997 AC: 293 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 68015 AN: 68036

Other (OTH) AF: 0.978 AC: 2067 AN: 2114

Alfa AF: 0.988 Hom.: 147759

Bravo AF: 0.961

TwinsUK AF: 1.00 AC: 3708

ALSPAC AF: 1.00 AC: 3854

ESP6500AA AF: 0.884 AC: 3339

ESP6500EA AF: 1.00 AC: 8247

ExAC AF: 0.989 AC: 119492

Asia WGS AF: 0.991 AC: 3447 AN: 3478

EpiCase AF: 1.00

EpiControl AF: 1.00

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	DNAH7-related disorder (1)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.045
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	22
DANN	Benign	0.40
DEOGEN2	Benign	0.013	T
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.028	N
LIST_S2	Benign	0.41	T
MetaRNN	Benign	6.8e-7	T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	-4.0	N
PhyloP100		7.6
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	9.5	N
REVEL	Benign	0.25
Sift	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.068
MPC		0.039
ClinPred		0.020	T
GERP RS		5.1
Varity_R		0.093
gMVP		0.56
Mutation Taster		=95/5	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: rs13411834; hg19: chr2-196673533; COSMIC: COSV107351535;