NM_001277115.2:c.939C>T

Variant names:

• chr7-21561127-C-T
• rs72655977
• NM_001277115.2:c.939C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6 BP7 BS1 BS2

The NM_001277115.2(DNAH11):​c.939C>T​(p.Ser313Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00758 in 1,604,034 control chromosomes in the GnomAD database, including 69 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0050 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0079 (68 hom.)
• Consequence: DNAH11 NM_001277115.2 synonymous
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:7
• Conservation: PhyloP100: 0.858
• Publications: 5 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]

DNAH11 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia 7

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), ClinGen
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

LOC105375183 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BP6: Variant 7-21561127-C-T is Benign according to our data. Variant chr7-21561127-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 178722.
• BP7: Synonymous conserved (PhyloP=0.858 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00504 (767/152258) while in subpopulation NFE AF = 0.00851 (579/68022). AF 95% confidence interval is 0.00794. There are 1 homozygotes in GnomAd4. There are 393 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 68 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.939C>T	p.Ser313Ser	synonymous	Exon 5 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.939C>T	p.Ser313Ser	synonymous	Exon 5 of 82	ENSP00000475939.1
	DNAH11	ENST00000483691.1	TSL:3	n.135C>T		non_coding_transcript_exon	Exon 2 of 2
	DNAH11	ENST00000496218.1	TSL:2	n.37C>T		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.00504 AC: 767 AN: 152140 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00128

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.000851

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00228

Gnomad FIN AF: 0.00801

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00851

Gnomad OTH AF: 0.00478

GnomAD2 exomes AF: 0.00457 AC: 1069 AN: 233692 AF XY: 0.00471

Gnomad AFR exome AF: 0.000968

Gnomad AMR exome AF: 0.00127

Gnomad ASJ exome AF: 0.000308

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00790

Gnomad NFE exome AF: 0.00742

Gnomad OTH exome AF: 0.00524

GnomAD4 exome AF: 0.00785 AC: 11398 AN: 1451776 Hom.: 68 Cov.: 30 AF XY: 0.00767 AC XY: 5531 AN XY: 720840

African (AFR) AF: 0.00132 AC: 44 AN: 33356

American (AMR) AF: 0.00122 AC: 53 AN: 43546

Ashkenazi Jewish (ASJ) AF: 0.000270 AC: 7 AN: 25940

East Asian (EAS) AF: 0.00 AC: 0 AN: 39418

South Asian (SAS) AF: 0.00143 AC: 120 AN: 83992

European-Finnish (FIN) AF: 0.00884 AC: 467 AN: 52834

Middle Eastern (MID) AF: 0.000348 AC: 2 AN: 5754

European-Non Finnish (NFE) AF: 0.00933 AC: 10332 AN: 1106926

Other (OTH) AF: 0.00622 AC: 373 AN: 60010

GnomAD4 genome AF: 0.00504 AC: 767 AN: 152258 Hom.: 1 Cov.: 32 AF XY: 0.00528 AC XY: 393 AN XY: 74434

African (AFR) AF: 0.00128 AC: 53 AN: 41556

American (AMR) AF: 0.000850 AC: 13 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00228 AC: 11 AN: 4816

European-Finnish (FIN) AF: 0.00801 AC: 85 AN: 10606

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

European-Non Finnish (NFE) AF: 0.00851 AC: 579 AN: 68022

Other (OTH) AF: 0.00473 AC: 10 AN: 2114

Alfa AF: 0.00645 Hom.: 3

Bravo AF: 0.00430

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	not provided (2)
-	1	1	Primary ciliary dyskinesia (2)
-	-	1	Primary ciliary dyskinesia 7 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	7.6
DANN	Benign	0.68
PhyloP100		0.86
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: rs72655977; hg19: chr7-21600745;