rs143362381

Variant names:

• chr7-21901198-G-A
• rs143362381
• NM_001277115.2:c.13495G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-21901198-G-A
• chr7-21901198-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001277115.2(DNAH11):​c.13495G>A​(p.Glu4499Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00367 in 1,613,662 control chromosomes in the GnomAD database, including 50 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E4499D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0040 (7 hom., cov: 33)
  • Exomes 𝑓: 0.0036 (43 hom.)
• Consequence: DNAH11 NM_001277115.2 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 1.04
• Publications: 10 publications found

Genes affected

DNAH11 (HGNC:2942): (dynein axonemal heavy chain 11) This gene encodes a ciliary outer dynein arm protein and is a member of the dynein heavy chain family. It is a microtubule-dependent motor ATPase and has been reported to be involved in the movement of respiratory cilia. Mutations in this gene have been implicated in causing Kartagener Syndrome (a combination of situs inversus totalis and Primary Ciliary Dyskinesia (PCD), also called Immotile Cilia Syndrome 1 (ICS1)) and male sterility. [provided by RefSeq, Mar 2013]

CDCA7L (HGNC:30777): (cell division cycle associated 7 like) Acts upstream of or within positive regulation of cell population proliferation. Located in cytosol; fibrillar center; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.002060622).
• BP6: Variant 7-21901198-G-A is Benign according to our data. Variant chr7-21901198-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 226581.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.00363 (5312/1461600) while in subpopulation MID AF = 0.00433 (25/5768). AF 95% confidence interval is 0.00308. There are 43 homozygotes in GnomAdExome4. There are 2634 alleles in the male GnomAdExome4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 7 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001277115.2. 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
	DNAH11	NM_001277115.2	MANE Select	c.13495G>A	p.Glu4499Lys	missense	Exon 82 of 82	NP_001264044.1	Q96DT5
	CDCA7L	NM_018719.5	MANE Select	c.*1124C>T		3_prime_UTR	Exon 10 of 10	NP_061189.2
	CDCA7L	NM_001127370.3		c.*1124C>T		3_prime_UTR	Exon 11 of 11	NP_001120842.1	Q96GN5-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH11	ENST00000409508.8	TSL:5 MANE Select	c.13495G>A	p.Glu4499Lys	missense	Exon 82 of 82	ENSP00000475939.1	Q96DT5
	CDCA7L	ENST00000406877.8	TSL:1 MANE Select	c.*1124C>T		3_prime_UTR	Exon 10 of 10	ENSP00000383986.3	Q96GN5-1
	CDCA7L	ENST00000934293.1		c.*1124C>T		3_prime_UTR	Exon 10 of 10	ENSP00000604352.1

Frequencies

GnomAD3 genomes AF: 0.00398 AC: 604 AN: 151946 Hom.: 7 Cov.: 33

Gnomad AFR AF: 0.000676

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00242

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00193

Gnomad SAS AF: 0.00314

Gnomad FIN AF: 0.0290

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00297

Gnomad OTH AF: 0.00192

GnomAD2 exomes AF: 0.00458 AC: 1131 AN: 247058 AF XY: 0.00450

Gnomad AFR exome AF: 0.000517

Gnomad AMR exome AF: 0.00122

Gnomad ASJ exome AF: 0.000298

Gnomad EAS exome AF: 0.00217

Gnomad FIN exome AF: 0.0269

Gnomad NFE exome AF: 0.00330

Gnomad OTH exome AF: 0.00298

GnomAD4 exome AF: 0.00363 AC: 5312 AN: 1461600 Hom.: 43 Cov.: 33 AF XY: 0.00362 AC XY: 2634 AN XY: 727068

African (AFR) AF: 0.000777 AC: 26 AN: 33476

American (AMR) AF: 0.00119 AC: 53 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000383 AC: 10 AN: 26134

East Asian (EAS) AF: 0.00166 AC: 66 AN: 39698

South Asian (SAS) AF: 0.00249 AC: 215 AN: 86214

European-Finnish (FIN) AF: 0.0232 AC: 1237 AN: 53402

Middle Eastern (MID) AF: 0.00433 AC: 25 AN: 5768

European-Non Finnish (NFE) AF: 0.00316 AC: 3518 AN: 1111816

Other (OTH) AF: 0.00268 AC: 162 AN: 60368

GnomAD4 genome AF: 0.00397 AC: 604 AN: 152062 Hom.: 7 Cov.: 33 AF XY: 0.00518 AC XY: 385 AN XY: 74340

African (AFR) AF: 0.000674 AC: 28 AN: 41522

American (AMR) AF: 0.00242 AC: 37 AN: 15292

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

East Asian (EAS) AF: 0.00194 AC: 10 AN: 5164

South Asian (SAS) AF: 0.00314 AC: 15 AN: 4780

European-Finnish (FIN) AF: 0.0290 AC: 307 AN: 10588

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00297 AC: 202 AN: 67942

Other (OTH) AF: 0.00190 AC: 4 AN: 2106

Alfa AF: 0.00258 Hom.: 3

Bravo AF: 0.00193

TwinsUK AF: 0.00216 AC: 8

ALSPAC AF: 0.00415 AC: 16

ESP6500AA AF: 0.000782 AC: 3

ESP6500EA AF: 0.00253 AC: 21

ExAC AF: 0.00400 AC: 484

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.00207

EpiControl AF: 0.00344

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	2	Primary ciliary dyskinesia (2)
-	-	1	Primary ciliary dyskinesia 7 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	6.1
DANN	Benign	0.66
DEOGEN2	Benign	0.013	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.048	N
LIST_S2	Benign	0.52	T
MetaRNN	Benign	0.0021	T
MetaSVM	Benign	-0.90	T
PhyloP100		1.0
PrimateAI	Benign	0.28	T
PROVEAN	Benign	3.1	N
REVEL	Benign	0.032
Sift	Benign	1.0	T
Vest4		0.16
MVP		0.085
ClinPred		0.0019	T
GERP RS		0.46
Varity_R		0.025
gMVP		0.16
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs143362381; hg19: chr7-21940816; COSMIC: COSV99050047; COSMIC: COSV99050047;