rs4392792

Variant names:

• chr7-21564268-A-G
• rs4392792
• NM_001277115.2:c.1065A>G

Your query was ambiguous. Multiple possible variants found:

• chr7-21564268-A-G
• chr7-21564268-A-C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001277115.2(DNAH11):​c.1065A>G​(p.Pro355Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0679 in 1,613,430 control chromosomes in the GnomAD database, including 9,200 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1994 hom., cov: 32)
  • Exomes 𝑓: 0.062 (7206 hom.)
• Consequence: DNAH11 NM_001277115.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.290
• Publications: 14 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: Labcorp Genetics (formerly Invitae), ClinGen, Laboratory for Molecular Medicine
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

LOC105375183 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 7-21564268-A-G is Benign according to our data. Variant chr7-21564268-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 178723.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.29 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.311 is higher than 0.05.

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.1065A>G	p.Pro355Pro	synonymous	Exon 6 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.1065A>G	p.Pro355Pro	synonymous	Exon 6 of 82	ENSP00000475939.1	Q96DT5
	DNAH11	ENST00000496218.1	TSL:2	n.80+3098A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18895 AN: 152024 Hom.: 1982 Cov.: 32

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.0234

Gnomad EAS AF: 0.326

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.0597

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0368

Gnomad OTH AF: 0.0982

GnomAD2 exomes AF: 0.126 AC: 31307 AN: 248596 AF XY: 0.114

Gnomad AFR exome AF: 0.236

Gnomad AMR exome AF: 0.330

Gnomad ASJ exome AF: 0.0236

Gnomad EAS exome AF: 0.330

Gnomad FIN exome AF: 0.0583

Gnomad NFE exome AF: 0.0371

Gnomad OTH exome AF: 0.0899

GnomAD4 exome AF: 0.0620 AC: 90601 AN: 1461288 Hom.: 7206 Cov.: 32 AF XY: 0.0623 AC XY: 45267 AN XY: 726902

African (AFR) AF: 0.233 AC: 7789 AN: 33466

American (AMR) AF: 0.318 AC: 14201 AN: 44654

Ashkenazi Jewish (ASJ) AF: 0.0209 AC: 546 AN: 26132

East Asian (EAS) AF: 0.294 AC: 11663 AN: 39668

South Asian (SAS) AF: 0.134 AC: 11544 AN: 86214

European-Finnish (FIN) AF: 0.0591 AC: 3154 AN: 53382

Middle Eastern (MID) AF: 0.0790 AC: 455 AN: 5762

European-Non Finnish (NFE) AF: 0.0327 AC: 36336 AN: 1111662

Other (OTH) AF: 0.0814 AC: 4913 AN: 60348

GnomAD4 genome AF: 0.125 AC: 18953 AN: 152142 Hom.: 1994 Cov.: 32 AF XY: 0.130 AC XY: 9648 AN XY: 74396

African (AFR) AF: 0.234 AC: 9711 AN: 41496

American (AMR) AF: 0.223 AC: 3401 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0234 AC: 81 AN: 3468

East Asian (EAS) AF: 0.324 AC: 1676 AN: 5168

South Asian (SAS) AF: 0.147 AC: 708 AN: 4818

European-Finnish (FIN) AF: 0.0597 AC: 633 AN: 10600

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0368 AC: 2501 AN: 67996

Other (OTH) AF: 0.100 AC: 211 AN: 2110

Alfa AF: 0.0796 Hom.: 893

Bravo AF: 0.142

Asia WGS AF: 0.267 AC: 929 AN: 3476

EpiCase AF: 0.0355

EpiControl AF: 0.0361

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)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	1.0
DANN	Benign	0.50
PhyloP100		-0.29
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: rs4392792; hg19: chr7-21603886; COSMIC: COSV60943908; COSMIC: COSV60943908;