2-26402004-G-C

Variant names:

• chr2-26402004-G-C
• rs746939507
• NM_145038.5:c.15G>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_145038.5(DRC1):​c.15G>C​(p.Gly5Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,692 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. G5G) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: DRC1 NM_145038.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.190
• Publications: 0 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP7: Synonymous conserved (PhyloP=-0.19 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DRC1	NM_145038.5	c.15G>C	p.Gly5Gly	synonymous_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.15G>C	p.Gly5Gly	synonymous_variant	Exon 1 of 17	2	NM_145038.5	ENSP00000288710.2
DRC1	ENST00000421869.5	n.15G>C		non_coding_transcript_exon_variant	Exon 1 of 8	1		ENSP00000414375.1
DRC1	ENST00000649059.1	n.-1G>C		non_coding_transcript_exon_variant	Exon 1 of 16			ENSP00000497543.1
DRC1	ENST00000649059.1	n.-1G>C		5_prime_UTR_variant	Exon 1 of 16			ENSP00000497543.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455692 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 723496

African (AFR) AF: 0.00 AC: 0 AN: 33374

American (AMR) AF: 0.00 AC: 0 AN: 44144

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25918

East Asian (EAS) AF: 0.00 AC: 0 AN: 39468

South Asian (SAS) AF: 0.00 AC: 0 AN: 84830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52522

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1109564

Other (OTH) AF: 0.00 AC: 0 AN: 60116

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	5.8
DANN	Benign	0.76
PhyloP100		-0.19
PromoterAI		0.034	Neutral
Mutation Taster		=100/0	polymorphism

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: rs746939507; hg19: chr2-26624872;