rs150682314

Variant names:

• chr7-21901008-C-T
• rs150682314
• NM_001277115.2:c.13305C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-21901008-C-T
• chr7-21901008-C-A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6 BP7 BS2

The NM_001277115.2(DNAH11):​c.13305C>T​(p.Gly4435Gly) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000376 in 1,586,380 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.00036 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00038 (2 hom.)
• Consequence: DNAH11 NM_001277115.2 splice_region, synonymous
• Scores: Splicing: ADA: 0.00002131
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:3 B:6
• Conservation: PhyloP100: -0.744
• Publications: 3 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP6: Variant 7-21901008-C-T is Benign according to our data. Variant chr7-21901008-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 257872.
• BP7: Synonymous conserved (PhyloP=-0.744 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 2 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.13305C>T	p.Gly4435Gly	splice_region synonymous	Exon 82 of 82	NP_001264044.1	Q96DT5
	CDCA7L	NM_018719.5	MANE Select	c.*1314G>A		3_prime_UTR	Exon 10 of 10	NP_061189.2
	CDCA7L	NM_001127370.3		c.*1314G>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.13305C>T	p.Gly4435Gly	splice_region synonymous	Exon 82 of 82	ENSP00000475939.1	Q96DT5
	CDCA7L	ENST00000406877.8	TSL:1 MANE Select	c.*1314G>A		3_prime_UTR	Exon 10 of 10	ENSP00000383986.3	Q96GN5-1
	CDCA7L	ENST00000934293.1		c.*1314G>A		3_prime_UTR	Exon 10 of 10	ENSP00000604352.1

Frequencies

GnomAD3 genomes AF: 0.000368 AC: 56 AN: 152168 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000265

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000524

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.000957

GnomAD2 exomes AF: 0.000685 AC: 158 AN: 230680 AF XY: 0.000783

Gnomad AFR exome AF: 0.000198

Gnomad AMR exome AF: 0.000366

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00250

Gnomad FIN exome AF: 0.0000479

Gnomad NFE exome AF: 0.000281

Gnomad OTH exome AF: 0.00110

GnomAD4 exome AF: 0.000378 AC: 542 AN: 1434094 Hom.: 2 Cov.: 33 AF XY: 0.000436 AC XY: 310 AN XY: 710822

African (AFR) AF: 0.000247 AC: 8 AN: 32336

American (AMR) AF: 0.000325 AC: 13 AN: 39968

Ashkenazi Jewish (ASJ) AF: 0.0000406 AC: 1 AN: 24650

East Asian (EAS) AF: 0.00112 AC: 44 AN: 39278

South Asian (SAS) AF: 0.00278 AC: 227 AN: 81760

European-Finnish (FIN) AF: 0.0000757 AC: 4 AN: 52868

Middle Eastern (MID) AF: 0.00178 AC: 10 AN: 5628

European-Non Finnish (NFE) AF: 0.000178 AC: 195 AN: 1098484

Other (OTH) AF: 0.000677 AC: 40 AN: 59122

GnomAD4 genome AF: 0.000361 AC: 55 AN: 152286 Hom.: 0 Cov.: 33 AF XY: 0.000443 AC XY: 33 AN XY: 74464

African (AFR) AF: 0.000265 AC: 11 AN: 41554

American (AMR) AF: 0.000523 AC: 8 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00232 AC: 12 AN: 5174

South Asian (SAS) AF: 0.00186 AC: 9 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

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

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 68026

Other (OTH) AF: 0.000947 AC: 2 AN: 2112

Alfa AF: 0.000339 Hom.: 1

Bravo AF: 0.000321

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	2	2	not provided (4)
-	1	2	Primary ciliary dyskinesia (3)
-	-	1	not specified (1)
-	-	1	Primary ciliary dyskinesia 7 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	0.73
DANN	Benign	0.73
PhyloP100		-0.74
Mutation Taster		=72/28	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000021
dbscSNV1_RF	Benign	0.010
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: rs150682314; hg19: chr7-21940626;