rs72658840

Variant names:

• chr7-21901250-C-T
• rs72658840
• NM_001277115.2:c.13547C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-21901250-C-T
• chr7-21901250-C-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001277115.2(DNAH11):​c.13547C>T​(p.Ala4516Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00536 in 1,601,468 control chromosomes in the GnomAD database, including 310 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict 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. A4516A) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.026 (170 hom., cov: 32)
  • Exomes 𝑓: 0.0032 (140 hom.)
• Consequence: DNAH11 NM_001277115.2 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 2.62
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0014667213).
• BP6: Variant 7-21901250-C-T is Benign according to our data. Variant chr7-21901250-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 226582.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0862 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.13547C>T	p.Ala4516Val	missense	Exon 82 of 82	NP_001264044.1	Q96DT5
	CDCA7L	NM_018719.5	MANE Select	c.*1072G>A		3_prime_UTR	Exon 10 of 10	NP_061189.2
	CDCA7L	NM_001127370.3		c.*1072G>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.13547C>T	p.Ala4516Val	missense	Exon 82 of 82	ENSP00000475939.1	Q96DT5
	CDCA7L	ENST00000406877.8	TSL:1 MANE Select	c.*1072G>A		3_prime_UTR	Exon 10 of 10	ENSP00000383986.3	Q96GN5-1
	CDCA7L	ENST00000934293.1		c.*1072G>A		3_prime_UTR	Exon 10 of 10	ENSP00000604352.1

Frequencies

GnomAD3 genomes AF: 0.0262 AC: 3847 AN: 146778 Hom.: 169 Cov.: 32

Gnomad AFR AF: 0.0888

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00951

Gnomad ASJ AF: 0.00180

Gnomad EAS AF: 0.000609

Gnomad SAS AF: 0.00193

Gnomad FIN AF: 0.000194

Gnomad MID AF: 0.00323

Gnomad NFE AF: 0.000931

Gnomad OTH AF: 0.0189

GnomAD2 exomes AF: 0.00685 AC: 1641 AN: 239448 AF XY: 0.00522

Gnomad AFR exome AF: 0.0867

Gnomad AMR exome AF: 0.00476

Gnomad ASJ exome AF: 0.00157

Gnomad EAS exome AF: 0.000113

Gnomad FIN exome AF: 0.000142

Gnomad NFE exome AF: 0.000818

Gnomad OTH exome AF: 0.00462

GnomAD4 exome AF: 0.00325 AC: 4724 AN: 1454598 Hom.: 140 Cov.: 33 AF XY: 0.00282 AC XY: 2040 AN XY: 722758

African (AFR) AF: 0.0855 AC: 2845 AN: 33268

American (AMR) AF: 0.00532 AC: 236 AN: 44348

Ashkenazi Jewish (ASJ) AF: 0.00171 AC: 44 AN: 25768

East Asian (EAS) AF: 0.000355 AC: 14 AN: 39458

South Asian (SAS) AF: 0.000758 AC: 64 AN: 84428

European-Finnish (FIN) AF: 0.000226 AC: 12 AN: 53202

Middle Eastern (MID) AF: 0.00418 AC: 24 AN: 5740

European-Non Finnish (NFE) AF: 0.000950 AC: 1053 AN: 1108328

Other (OTH) AF: 0.00719 AC: 432 AN: 60058

GnomAD4 genome AF: 0.0262 AC: 3855 AN: 146870 Hom.: 170 Cov.: 32 AF XY: 0.0247 AC XY: 1775 AN XY: 71742

African (AFR) AF: 0.0886 AC: 3587 AN: 40478

American (AMR) AF: 0.00949 AC: 143 AN: 15064

Ashkenazi Jewish (ASJ) AF: 0.00180 AC: 6 AN: 3326

East Asian (EAS) AF: 0.000610 AC: 3 AN: 4918

South Asian (SAS) AF: 0.00145 AC: 6 AN: 4138

European-Finnish (FIN) AF: 0.000194 AC: 2 AN: 10332

Middle Eastern (MID) AF: 0.00345 AC: 1 AN: 290

European-Non Finnish (NFE) AF: 0.000931 AC: 61 AN: 65530

Other (OTH) AF: 0.0227 AC: 46 AN: 2026

Alfa AF: 0.0218 Hom.: 103

Bravo AF: 0.0285

TwinsUK AF: 0.00135 AC: 5

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.0761 AC: 301

ESP6500EA AF: 0.00144 AC: 12

ExAC AF: 0.00768 AC: 928

Asia WGS AF: 0.0240 AC: 84 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	15
DANN	Benign	0.97
DEOGEN2	Benign	0.012	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.052	N
LIST_S2	Benign	0.79	T
MetaRNN	Benign	0.0015	T
MetaSVM	Benign	-1.0	T
PhyloP100		2.6
PrimateAI	Benign	0.40	T
PROVEAN	Benign	1.7	N
REVEL	Benign	0.15
Sift	Benign	0.17	T
Vest4		0.12
MVP		0.014
ClinPred		0.0098	T
GERP RS		3.8
Varity_R		0.047
gMVP		0.17
Mutation Taster		=99/1	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: rs72658840; hg19: chr7-21940868;