NM_018897.3:c.11843A>G

Variant names:

• chr2-195740791-T-C
• rs374466394
• NM_018897.3:c.11843A>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_018897.3(DNAH7):​c.11843A>G​(p.Lys3948Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000714 in 1,401,374 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: DNAH7 NM_018897.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.36
• Publications: 0 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: ClinGen, 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

LOC107985972 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.11843A>G	p.Lys3948Arg	missense	Exon 64 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.11843A>G	p.Lys3948Arg	missense	Exon 64 of 65	ENSP00000311273.6	Q8WXX0-1
	DNAH7	ENST00000409063.5	TSL:1	c.1292A>G	p.Lys431Arg	missense	Exon 9 of 10	ENSP00000386912.1	Q8WXX0-2
	DNAH7	ENST00000438565.1	TSL:3	c.145A>G	p.Lys49Glu	missense	Exon 2 of 3	ENSP00000409732.1	H7C362

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD2 exomes AF: 0.00000441 AC: 1 AN: 226580 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000946

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.14e-7 AC: 1 AN: 1401374 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 695580

African (AFR) AF: 0.00 AC: 0 AN: 31746

American (AMR) AF: 0.00 AC: 0 AN: 39496

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24784

East Asian (EAS) AF: 0.00 AC: 0 AN: 37050

South Asian (SAS) AF: 0.00 AC: 0 AN: 73764

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50962

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5548

European-Non Finnish (NFE) AF: 9.25e-7 AC: 1 AN: 1080706

Other (OTH) AF: 0.00 AC: 0 AN: 57318

GnomAD4 genome Cov.: 30

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000123 AC: 1

ExAC AF: 0.00000828 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Benign	-0.40
CADD	Benign	22
DANN	Uncertain	1.0
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.25	T
M_CAP	Benign	0.031	D
MetaRNN	Uncertain	0.46	T
MetaSVM	Benign	-1.2	T
PhyloP100		5.4
PROVEAN	Benign	-0.17	N
REVEL	Benign	0.20
MVP		0.45
ClinPred		0.96	D
GERP RS		4.8
Varity_R		0.37
Mutation Taster		=71/29	polymorphism

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: rs374466394; hg19: chr2-196605515; COSMIC: COSV100414841; COSMIC: COSV100414841;