NM_018897.3:c.12041G>A

Variant names:

• chr2-195737955-C-T
• rs200224437
• NM_018897.3:c.12041G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_018897.3(DNAH7):​c.12041G>A​(p.Arg4014Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000219 in 1,614,070 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0011 (2 hom., cov: 33)
  • Exomes 𝑓: 0.00013 (1 hom.)
• Consequence: DNAH7 NM_018897.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 6.13
• 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]

SLC39A10 (HGNC:20861): (solute carrier family 39 member 10) Zinc is an essential cofactor for hundreds of enzymes. It is involved in protein, nucleic acid, carbohydrate, and lipid metabolism, as well as in the control of gene transcription, growth, development, and differentiation. SLC39A10 belongs to a subfamily of proteins that show structural characteristics of zinc transporters (Taylor and Nicholson, 2003 [PubMed 12659941]).[supplied by OMIM, Mar 2008]

LOC107985972 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.027631223).
• BP6: Variant 2-195737955-C-T is Benign according to our data. Variant chr2-195737955-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 732940.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00112 (171/152332) while in subpopulation AFR AF = 0.00387 (161/41582). AF 95% confidence interval is 0.00338. There are 2 homozygotes in GnomAd4. There are 83 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

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.12041G>A	p.Arg4014Gln	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.12041G>A	p.Arg4014Gln	missense	Exon 65 of 65	ENSP00000311273.6	Q8WXX0-1
	DNAH7	ENST00000409063.5	TSL:1	c.1490G>A	p.Arg497Gln	missense	Exon 10 of 10	ENSP00000386912.1	Q8WXX0-2
	DNAH7	ENST00000484183.1	TSL:2	n.539G>A		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.00113 AC: 172 AN: 152214 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.00391

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.000321 AC: 80 AN: 249404 AF XY: 0.000244

Gnomad AFR exome AF: 0.00465

Gnomad AMR exome AF: 0.0000869

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000167

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000177

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000125 AC: 183 AN: 1461738 Hom.: 1 Cov.: 32 AF XY: 0.000105 AC XY: 76 AN XY: 727182

African (AFR) AF: 0.00415 AC: 139 AN: 33480

American (AMR) AF: 0.000157 AC: 7 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.000151 AC: 6 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000126 AC: 14 AN: 1111894

Other (OTH) AF: 0.000265 AC: 16 AN: 60386

GnomAD4 genome AF: 0.00112 AC: 171 AN: 152332 Hom.: 2 Cov.: 33 AF XY: 0.00111 AC XY: 83 AN XY: 74490

African (AFR) AF: 0.00387 AC: 161 AN: 41582

American (AMR) AF: 0.000327 AC: 5 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68030

Other (OTH) AF: 0.00142 AC: 3 AN: 2116

Alfa AF: 0.000539 Hom.: 0

Bravo AF: 0.00139

ESP6500AA AF: 0.00260 AC: 10

ESP6500EA AF: 0.000121 AC: 1

ExAC AF: 0.000389 AC: 47

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.45
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Uncertain	0.020
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.040	T
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.075	D
MetaRNN	Benign	0.028	T
MetaSVM	Uncertain	0.031	D
MutationAssessor	Uncertain	2.6	M
PhyloP100		6.1
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-3.9	D
REVEL	Uncertain	0.43
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.011	D
Polyphen		1.0	D
Vest4		0.70
MVP		0.57
MPC		0.25
ClinPred		0.19	T
GERP RS		4.5
Varity_R		0.76
gMVP		0.81
Mutation Taster		=90/10	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: rs200224437; hg19: chr2-196602679; COSMIC: COSV56753121; COSMIC: COSV56753121;