Genetic Variant DRC1:p.Ala24Val (chr2-26402060-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_145038.5(DRC1):c.71C>T(p.Ala24Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,058 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A24E) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

DRC1
NM_145038.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.110

Publications

0 publications found

Variant links:

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: DEFINITIVE, STRONG, MODERATE Submitted by: ClinGen, Ambry Genetics, G2P, 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

DRC1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.030399323).

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.71C>T	p.Ala24Val	missense	Exon 1 of 17	NP_659475.2	Q96MC2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DRC1	ENST00000288710.7	TSL:2 MANE Select	c.71C>T	p.Ala24Val	missense	Exon 1 of 17	ENSP00000288710.2	Q96MC2
DRC1	ENST00000421869.5	TSL:1	n.71C>T		non_coding_transcript_exon	Exon 1 of 8	ENSP00000414375.1	F8WE02
DRC1	ENST00000868388.1		c.71C>T	p.Ala24Val	missense	Exon 1 of 17	ENSP00000538447.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461058

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726822

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33462

American (AMR)

AF:

0.00

AC:

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26116

East Asian (EAS)

AF:

0.00

AC:

AN:

39670

South Asian (SAS)

AF:

0.00

AC:

AN:

86210

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52980

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111798

Other (OTH)

AF:

0.00

AC:

AN:

60356

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.81

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.0026

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.078

LIST_S2

Benign

0.40

M_CAP

Benign

0.0024

MetaRNN

Benign

0.030

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.34

PhyloP100

-0.11

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.5

REVEL

Benign

0.029

Sift

Benign

0.21

Sift4G

Benign

0.20

Polyphen

0.013

Vest4

0.042

MutPred

0.13

Loss of loop (P = 0.1258)

MVP

0.055

MPC

0.057

ClinPred

0.056

GERP RS

-2.7

PromoterAI

0.050

Neutral

(source)

Varity_R

0.042

gMVP

0.30

Mutation Taster

=97/3

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over