2-26402072-A-T

Variant names:

• chr2-26402072-A-T
• rs771532771
• NM_145038.5:c.83A>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_145038.5(DRC1):​c.83A>T​(p.His28Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 151,916 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.000013 (0 hom., cov: 32)
• Consequence: DRC1 NM_145038.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.96

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06196189).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DRC1	NM_145038.5	c.83A>T	p.His28Leu	missense_variant	Exon 1 of 17	ENST00000288710.7	NP_659475.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DRC1	ENST00000288710.7	c.83A>T	p.His28Leu	missense_variant	Exon 1 of 17	2	NM_145038.5	ENSP00000288710.2
DRC1	ENST00000421869.5	n.83A>T		non_coding_transcript_exon_variant	Exon 1 of 8	1		ENSP00000414375.1
DRC1	ENST00000649059.1	n.68A>T		non_coding_transcript_exon_variant	Exon 1 of 16			ENSP00000497543.1

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151916 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000484

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151916 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74194

Gnomad4 AFR AF: 0.0000484

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	14
DANN	Benign	0.59
DEOGEN2	Benign	0.026	T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.062	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.60	N
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.058
Sift	Benign	0.13	T
Sift4G	Benign	0.65	T
Polyphen		0.0	B
Vest4		0.20
MutPred		0.16		Loss of MoRF binding (P = 0.1163);
MVP		0.14
MPC		0.067
ClinPred		0.069	T
GERP RS		2.6
Varity_R		0.21
gMVP		0.28

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

LitVar

Other links and lift over

dbSNP: rs771532771; hg19: chr2-26624940;