2-26401950-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_145038.5(DRC1):c.-40T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00193 in 1,560,252 control chromosomes in the GnomAD database, including 57 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.010 (31 hom., cov: 32)
  • Exomes 𝑓: 0.0010 (26 hom.)
• Consequence: DRC1 NM_145038.5 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.784

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 2-26401950-T-C is Benign according to our data. Variant chr2-26401950-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1203685.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0102 (1549/152210) while in subpopulation AFR AF= 0.0351 (1459/41514). AF 95% confidence interval is 0.0336. There are 31 homozygotes in gnomad4. There are 738 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 31 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DRC1	NM_145038.5	c.-40T>C		5_prime_UTR_variant	1/17	ENST00000288710.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DRC1	ENST00000288710.7	c.-40T>C		5_prime_UTR_variant	1/17	2	NM_145038.5	P1
DRC1	ENST00000421869.5	c.-40T>C		5_prime_UTR_variant, NMD_transcript_variant	1/8	1

Frequencies

GnomAD3 genomes AF: 0.0102 AC: 1547 AN: 152092 Hom.: 31 Cov.: 32

Gnomad AFR AF: 0.0352

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00386

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00255 AC: 432 AN: 169150 Hom.: 8 AF XY: 0.00190 AC XY: 172 AN XY: 90714

Gnomad AFR exome AF: 0.0350

Gnomad AMR exome AF: 0.00199

Gnomad ASJ exome AF: 0.000243

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000423

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000207

Gnomad OTH exome AF: 0.00200

GnomAD4 exome AF: 0.00104 AC: 1468 AN: 1408042 Hom.: 26 Cov.: 30 AF XY: 0.000919 AC XY: 639 AN XY: 695548

Gnomad4 AFR exome AF: 0.0345

Gnomad4 AMR exome AF: 0.00210

Gnomad4 ASJ exome AF: 0.000161

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000138

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000109

Gnomad4 OTH exome AF: 0.00225

GnomAD4 genome AF: 0.0102 AC: 1549 AN: 152210 Hom.: 31 Cov.: 32 AF XY: 0.00992 AC XY: 738 AN XY: 74422

Gnomad4 AFR AF: 0.0351

Gnomad4 AMR AF: 0.00385

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000294

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00437 Hom.: 3

Bravo AF: 0.0118

Asia WGS AF: 0.00289 AC: 10 AN: 3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 02, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	1.4
Dann	Benign	0.36

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: rs114557669; hg19: chr2-26624818;