NM_001277115.2:c.13263G>C

Variant names:

• chr7-21900080-G-C
• rs72658834
• NM_001277115.2:c.13263G>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.13263G>C​(p.Pro4421Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0112 in 1,613,828 control chromosomes in the GnomAD database, including 166 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. P4421P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.010 (22 hom., cov: 33)
  • Exomes 𝑓: 0.011 (144 hom.)
• Consequence: DNAH11 NM_001277115.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -1.82
• Publications: 2 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=-0.61).
• BP6: Variant 7-21900080-G-C is Benign according to our data. Variant chr7-21900080-G-C is described in ClinVar as Benign. ClinVar VariationId is 163129.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.82 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0105 (1594/152240) while in subpopulation NFE AF = 0.0139 (945/68020). AF 95% confidence interval is 0.0132. There are 22 homozygotes in GnomAd4. There are 853 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 22 AD,AR 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.13263G>C	p.Pro4421Pro	synonymous	Exon 81 of 82	NP_001264044.1	Q96DT5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH11	ENST00000409508.8	TSL:5 MANE Select	c.13263G>C	p.Pro4421Pro	synonymous	Exon 81 of 82	ENSP00000475939.1	Q96DT5
	CDCA7L	ENST00000904741.1		c.*2242C>G		3_prime_UTR	Exon 10 of 10	ENSP00000574800.1
	DNAH11	ENST00000479878.1	TSL:3	n.634G>C		non_coding_transcript_exon	Exon 4 of 5

Frequencies

GnomAD3 genomes AF: 0.0105 AC: 1594 AN: 152122 Hom.: 22 Cov.: 33

Gnomad AFR AF: 0.00225

Gnomad AMI AF: 0.00659

Gnomad AMR AF: 0.00740

Gnomad ASJ AF: 0.00577

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.0377

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0139

Gnomad OTH AF: 0.00670

GnomAD2 exomes AF: 0.0110 AC: 2734 AN: 249016 AF XY: 0.0107

Gnomad AFR exome AF: 0.00175

Gnomad AMR exome AF: 0.00449

Gnomad ASJ exome AF: 0.00736

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0381

Gnomad NFE exome AF: 0.0139

Gnomad OTH exome AF: 0.0126

GnomAD4 exome AF: 0.0113 AC: 16548 AN: 1461588 Hom.: 144 Cov.: 31 AF XY: 0.0112 AC XY: 8115 AN XY: 727070

African (AFR) AF: 0.00134 AC: 45 AN: 33478

American (AMR) AF: 0.00470 AC: 210 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00712 AC: 186 AN: 26130

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

South Asian (SAS) AF: 0.000359 AC: 31 AN: 86244

European-Finnish (FIN) AF: 0.0363 AC: 1940 AN: 53386

Middle Eastern (MID) AF: 0.00312 AC: 18 AN: 5768

European-Non Finnish (NFE) AF: 0.0122 AC: 13517 AN: 1111794

Other (OTH) AF: 0.00996 AC: 601 AN: 60368

GnomAD4 genome AF: 0.0105 AC: 1594 AN: 152240 Hom.: 22 Cov.: 33 AF XY: 0.0115 AC XY: 853 AN XY: 74434

African (AFR) AF: 0.00224 AC: 93 AN: 41546

American (AMR) AF: 0.00739 AC: 113 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00577 AC: 20 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4820

European-Finnish (FIN) AF: 0.0377 AC: 399 AN: 10596

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

European-Non Finnish (NFE) AF: 0.0139 AC: 945 AN: 68020

Other (OTH) AF: 0.00664 AC: 14 AN: 2110

Alfa AF: 0.0108 Hom.: 16

Bravo AF: 0.00776

Asia WGS AF: 0.00202 AC: 7 AN: 3478

EpiCase AF: 0.0104

EpiControl AF: 0.00961

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	1	not provided (1)
-	-	1	Primary ciliary dyskinesia (1)
-	-	1	Primary ciliary dyskinesia 7 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	1.0
DANN	Benign	0.63
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

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: rs72658834; hg19: chr7-21939698;