rs115095929

Variant names:

• chr2-26455214-A-C
• rs115095929
• NM_145038.5:c.2147A>C

Your query was ambiguous. Multiple possible variants found:

• chr2-26455214-A-C
• chr2-26455214-A-G

Variant summary

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

The NM_145038.5(DRC1):​c.2147A>C​(p.Gln716Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0121 in 1,613,754 control chromosomes in the GnomAD database, including 808 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.017 (109 hom., cov: 32)
  • Exomes 𝑓: 0.012 (699 hom.)
• Consequence: DRC1 NM_145038.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 5.52
• Publications: 6 publications found

Genes affected

DRC1 (HGNC:24245): (dynein regulatory complex subunit 1) This gene encodes a central component of the nexin-dynein complex (N-DRC), which regulates the assembly of ciliary dynein. Mutations in this gene can cause ciliary dyskinesia. [provided by RefSeq, Aug 2015]

DRC1 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia 21

  Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• spermatogenic failure 80

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.003074348).
• BP6: Variant 2-26455214-A-C is Benign according to our data. Variant chr2-26455214-A-C is described in ClinVar as Benign. ClinVar VariationId is 414292.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0522 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145038.5. 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
	DRC1	NM_145038.5	MANE Select	c.2147A>C	p.Gln716Pro	missense	Exon 16 of 17	NP_659475.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DRC1	ENST00000288710.7	TSL:2 MANE Select	c.2147A>C	p.Gln716Pro	missense	Exon 16 of 17	ENSP00000288710.2
	DRC1	ENST00000868388.1		c.2072A>C	p.Gln691Pro	missense	Exon 16 of 17	ENSP00000538447.1
	DRC1	ENST00000941553.1		c.1850A>C	p.Gln617Pro	missense	Exon 14 of 15	ENSP00000611612.1

Frequencies

GnomAD3 genomes AF: 0.0174 AC: 2645 AN: 152182 Hom.: 108 Cov.: 32

Gnomad AFR AF: 0.00352

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0552

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0505

Gnomad SAS AF: 0.00394

Gnomad FIN AF: 0.0916

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00547

Gnomad OTH AF: 0.0153

GnomAD2 exomes AF: 0.0330 AC: 8281 AN: 250808 AF XY: 0.0272

Gnomad AFR exome AF: 0.00210

Gnomad AMR exome AF: 0.131

Gnomad ASJ exome AF: 0.000596

Gnomad EAS exome AF: 0.0505

Gnomad FIN exome AF: 0.0883

Gnomad NFE exome AF: 0.00583

Gnomad OTH exome AF: 0.0220

GnomAD4 exome AF: 0.0116 AC: 16911 AN: 1461454 Hom.: 699 Cov.: 32 AF XY: 0.0106 AC XY: 7734 AN XY: 726992

African (AFR) AF: 0.00161 AC: 54 AN: 33478

American (AMR) AF: 0.123 AC: 5491 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.000459 AC: 12 AN: 26132

East Asian (EAS) AF: 0.0426 AC: 1690 AN: 39698

South Asian (SAS) AF: 0.00320 AC: 276 AN: 86242

European-Finnish (FIN) AF: 0.0838 AC: 4465 AN: 53262

Middle Eastern (MID) AF: 0.00107 AC: 6 AN: 5614

European-Non Finnish (NFE) AF: 0.00377 AC: 4187 AN: 1111952

Other (OTH) AF: 0.0121 AC: 730 AN: 60362

GnomAD4 genome AF: 0.0174 AC: 2649 AN: 152300 Hom.: 109 Cov.: 32 AF XY: 0.0215 AC XY: 1599 AN XY: 74448

African (AFR) AF: 0.00351 AC: 146 AN: 41588

American (AMR) AF: 0.0553 AC: 846 AN: 15304

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

East Asian (EAS) AF: 0.0510 AC: 264 AN: 5178

South Asian (SAS) AF: 0.00394 AC: 19 AN: 4822

European-Finnish (FIN) AF: 0.0916 AC: 970 AN: 10584

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

European-Non Finnish (NFE) AF: 0.00547 AC: 372 AN: 68034

Other (OTH) AF: 0.0152 AC: 32 AN: 2112

Alfa AF: 0.00740 Hom.: 64

Bravo AF: 0.0173

TwinsUK AF: 0.00216 AC: 8

ALSPAC AF: 0.00182 AC: 7

ESP6500AA AF: 0.00409 AC: 18

ESP6500EA AF: 0.00302 AC: 26

ExAC AF: 0.0269 AC: 3268

Asia WGS AF: 0.0370 AC: 129 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.10
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.72	T
MetaRNN	Benign	0.0031	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		5.5
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.26
Sift	Uncertain	0.012	D
Sift4G	Benign	0.063	T
Polyphen		0.98	D
Vest4		0.21
MPC		0.27
ClinPred		0.037	T
GERP RS		4.2
Varity_R		0.92
gMVP		0.57
Mutation Taster		=95/5	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: rs115095929; hg19: chr2-26678082;