7-21899993-G-C

Variant names:

• chr7-21899993-G-C
• rs79449551
• NM_001277115.2:c.13176G>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001277115.2(DNAH11):​c.13176G>C​(p.Thr4392Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00159 in 1,613,794 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. T4392T) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0085 (21 hom., cov: 33)
  • Exomes 𝑓: 0.00088 (21 hom.)
• Consequence: DNAH11 NM_001277115.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.110
• Publications: 4 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 7-21899993-G-C is Benign according to our data. Variant chr7-21899993-G-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 221196.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.11 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00848 (1291/152194) while in subpopulation AFR AF = 0.0296 (1230/41512). AF 95% confidence interval is 0.0283. There are 21 homozygotes in GnomAd4. There are 596 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 21 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.13176G>C	p.Thr4392Thr	synonymous	Exon 81 of 82	NP_001264044.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH11	ENST00000409508.8	TSL:5 MANE Select	c.13176G>C	p.Thr4392Thr	synonymous	Exon 81 of 82	ENSP00000475939.1
	CDCA7L	ENST00000904741.1		c.*2329C>G		3_prime_UTR	Exon 10 of 10	ENSP00000574800.1
	DNAH11	ENST00000479878.1	TSL:3	n.547G>C		non_coding_transcript_exon	Exon 4 of 5

Frequencies

GnomAD3 genomes AF: 0.00846 AC: 1287 AN: 152076 Hom.: 21 Cov.: 33

Gnomad AFR AF: 0.0296

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00249

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00527

GnomAD2 exomes AF: 0.00207 AC: 516 AN: 249052 AF XY: 0.00167

Gnomad AFR exome AF: 0.0295

Gnomad AMR exome AF: 0.00113

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000886

Gnomad OTH exome AF: 0.00132

GnomAD4 exome AF: 0.000875 AC: 1279 AN: 1461600 Hom.: 21 Cov.: 31 AF XY: 0.000798 AC XY: 580 AN XY: 727084

African (AFR) AF: 0.0294 AC: 984 AN: 33476

American (AMR) AF: 0.00123 AC: 55 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.000139 AC: 12 AN: 86240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53396

Middle Eastern (MID) AF: 0.00295 AC: 17 AN: 5766

European-Non Finnish (NFE) AF: 0.0000756 AC: 84 AN: 1111810

Other (OTH) AF: 0.00210 AC: 127 AN: 60370

GnomAD4 genome AF: 0.00848 AC: 1291 AN: 152194 Hom.: 21 Cov.: 33 AF XY: 0.00801 AC XY: 596 AN XY: 74410

African (AFR) AF: 0.0296 AC: 1230 AN: 41512

American (AMR) AF: 0.00249 AC: 38 AN: 15278

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

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

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68016

Other (OTH) AF: 0.00522 AC: 11 AN: 2108

Alfa AF: 0.000440 Hom.: 0

Bravo AF: 0.00924

Asia WGS AF: 0.00202 AC: 7 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000297

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	1.4
DANN	Benign	0.76
PhyloP100		0.11
Mutation Taster		=100/0	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: rs79449551; hg19: chr7-21939611;