rs199706799

Variant names:

• chr7-21901080-C-T
• rs199706799
• NM_001277115.2:c.13377C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP6_Very_Strong BP7

The NM_001277115.2(DNAH11):​c.13377C>T​(p.Val4459Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000898 in 1,613,938 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00026 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000072 (0 hom.)
• Consequence: DNAH11 NM_001277115.2 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.86
• Publications: 0 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 7-21901080-C-T is Benign according to our data. Variant chr7-21901080-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 525472.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.86 with no splicing effect.

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.13377C>T	p.Val4459Val	synonymous	Exon 82 of 82	NP_001264044.1	Q96DT5
	CDCA7L	NM_018719.5	MANE Select	c.*1242G>A		3_prime_UTR	Exon 10 of 10	NP_061189.2
	CDCA7L	NM_001127370.3		c.*1242G>A		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.13377C>T	p.Val4459Val	synonymous	Exon 82 of 82	ENSP00000475939.1	Q96DT5
	CDCA7L	ENST00000406877.8	TSL:1 MANE Select	c.*1242G>A		3_prime_UTR	Exon 10 of 10	ENSP00000383986.3	Q96GN5-1
	CDCA7L	ENST00000934293.1		c.*1242G>A		3_prime_UTR	Exon 10 of 10	ENSP00000604352.1

Frequencies

GnomAD3 genomes AF: 0.000250 AC: 38 AN: 152202 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000796

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000124 AC: 31 AN: 249068 AF XY: 0.0000814

Gnomad AFR exome AF: 0.00110

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000975

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.0000718 AC: 105 AN: 1461618 Hom.: 0 Cov.: 33 AF XY: 0.0000605 AC XY: 44 AN XY: 727084

African (AFR) AF: 0.00122 AC: 41 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86224

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

Middle Eastern (MID) AF: 0.00139 AC: 8 AN: 5768

European-Non Finnish (NFE) AF: 0.0000315 AC: 35 AN: 1111820

Other (OTH) AF: 0.000282 AC: 17 AN: 60370

GnomAD4 genome AF: 0.000263 AC: 40 AN: 152320 Hom.: 0 Cov.: 33 AF XY: 0.000201 AC XY: 15 AN XY: 74484

African (AFR) AF: 0.000842 AC: 35 AN: 41572

American (AMR) AF: 0.0000654 AC: 1 AN: 15302

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

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

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

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68030

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.000134 Hom.: 0

Bravo AF: 0.000223

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	3.0
DANN	Benign	0.70
PhyloP100		1.9

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: rs199706799; hg19: chr7-21940698;