chr2-26401950-T-C

Variant names:

• chr2-26401950-T-C
• rs114557669
• NM_145038.5:c.-40T>C

Variant summary

Our verdict is Benign. The variant received -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
• 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: 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

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 31 AR,AD gene

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.-40T>C		5_prime_UTR	Exon 1 of 17	NP_659475.2	Q96MC2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DRC1	ENST00000288710.7	TSL:2 MANE Select	c.-40T>C		5_prime_UTR	Exon 1 of 17	ENSP00000288710.2	Q96MC2
	DRC1	ENST00000421869.5	TSL:1	n.-40T>C		non_coding_transcript_exon	Exon 1 of 8	ENSP00000414375.1	F8WE02
	DRC1	ENST00000421869.5	TSL:1	n.-40T>C		5_prime_UTR	Exon 1 of 8	ENSP00000414375.1	F8WE02

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

GnomAD2 exomes AF: 0.00255 AC: 432 AN: 169150 AF XY: 0.00190

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 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

African (AFR) AF: 0.0345 AC: 1112 AN: 32186

American (AMR) AF: 0.00210 AC: 78 AN: 37084

Ashkenazi Jewish (ASJ) AF: 0.000161 AC: 4 AN: 24828

East Asian (EAS) AF: 0.00 AC: 0 AN: 36946

South Asian (SAS) AF: 0.000138 AC: 11 AN: 79996

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49048

Middle Eastern (MID) AF: 0.00255 AC: 14 AN: 5492

European-Non Finnish (NFE) AF: 0.000109 AC: 118 AN: 1084262

Other (OTH) AF: 0.00225 AC: 131 AN: 58200

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

African (AFR) AF: 0.0351 AC: 1459 AN: 41514

American (AMR) AF: 0.00385 AC: 59 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000294 AC: 20 AN: 68004

Other (OTH) AF: 0.00237 AC: 5 AN: 2114

Alfa AF: 0.00443 Hom.: 4

Bravo AF: 0.0118

Asia WGS AF: 0.00289 AC: 10 AN: 3476

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.4
DANN	Benign	0.36
PhyloP100		-0.78
PromoterAI		0.11	Neutral
Mutation Taster		=300/0	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: rs114557669; hg19: chr2-26624818;