chr2-195738105-C-T

Variant names:

• chr2-195738105-C-T
• rs199830841
• NM_018897.3:c.11891G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_018897.3(DNAH7):​c.11891G>A​(p.Arg3964Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000359 in 1,613,844 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00024 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000015 (0 hom.)
• Consequence: DNAH7 NM_018897.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.155
• Publications: 1 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.009124279).

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.11891G>A	p.Arg3964Lys	missense	Exon 65 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.11891G>A	p.Arg3964Lys	missense	Exon 65 of 65	ENSP00000311273.6	Q8WXX0-1
	DNAH7	ENST00000409063.5	TSL:1	c.1340G>A	p.Arg447Lys	missense	Exon 10 of 10	ENSP00000386912.1	Q8WXX0-2
	DNAH7	ENST00000438565.1	TSL:3	c.*22G>A		3_prime_UTR	Exon 3 of 3	ENSP00000409732.1	H7C362

Frequencies

GnomAD3 genomes AF: 0.000237 AC: 36 AN: 152214 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000844

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000603 AC: 15 AN: 248906 AF XY: 0.0000444

Gnomad AFR exome AF: 0.000711

Gnomad AMR exome AF: 0.0000870

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000166

GnomAD4 exome AF: 0.0000151 AC: 22 AN: 1461512 Hom.: 0 Cov.: 32 AF XY: 0.0000165 AC XY: 12 AN XY: 727076

African (AFR) AF: 0.000538 AC: 18 AN: 33472

American (AMR) AF: 0.0000671 AC: 3 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 86240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111754

Other (OTH) AF: 0.0000166 AC: 1 AN: 60356

GnomAD4 genome AF: 0.000236 AC: 36 AN: 152332 Hom.: 0 Cov.: 33 AF XY: 0.000215 AC XY: 16 AN XY: 74484

African (AFR) AF: 0.000842 AC: 35 AN: 41584

American (AMR) AF: 0.00 AC: 0 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000128 Hom.: 0

Bravo AF: 0.000321

ESP6500AA AF: 0.00106 AC: 4

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000745 AC: 9

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	0.082
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	4.9
DANN	Benign	0.72
DEOGEN2	Benign	0.0050	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.060	N
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.0091	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	-0.33	N
PhyloP100		0.15
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.010	N
REVEL	Benign	0.0040
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.19
MVP		0.099
MPC		0.030
ClinPred		0.0058	T
GERP RS		0.62
Varity_R		0.055
gMVP		0.50
Mutation Taster		=94/6	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: rs199830841; hg19: chr2-196602829; COSMIC: COSV56777572; COSMIC: COSV56777572;