rs143407873

Variant names:

• chr2-19990398-C-A
• rs143407873
• ENST00000416575.3:n.234C>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The ENST00000416575.3(WDR35-DT):​n.234C>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0345 in 326,618 control chromosomes in the GnomAD database, including 273 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.032 (109 hom., cov: 33)
  • Exomes 𝑓: 0.037 (164 hom.)
• Consequence: WDR35-DT ENST00000416575.3 non_coding_transcript_exon
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.141
• Publications: 1 publications found

Genes affected

WDR35-DT (HGNC:55818): (WDR35 divergent transcript)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 2-19990398-C-A is Benign according to our data. Variant chr2-19990398-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1218452.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0315 (4802/152354) while in subpopulation NFE AF = 0.0444 (3018/68032). AF 95% confidence interval is 0.043. There are 109 homozygotes in GnomAd4. There are 2368 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 109 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000416575.3. 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
	WDR35-DT	NR_110235.1		n.195C>A		non_coding_transcript_exon	Exon 1 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR35-DT	ENST00000416575.3	TSL:2	n.234C>A		non_coding_transcript_exon	Exon 1 of 3
	WDR35-DT	ENST00000658200.1		n.190C>A		non_coding_transcript_exon	Exon 1 of 3
	WDR35-DT	ENST00000737626.1		n.214C>A		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes AF: 0.0315 AC: 4802 AN: 152236 Hom.: 109 Cov.: 33

Gnomad AFR AF: 0.00851

Gnomad AMI AF: 0.0647

Gnomad AMR AF: 0.0425

Gnomad ASJ AF: 0.0285

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0112

Gnomad FIN AF: 0.0441

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0444

Gnomad OTH AF: 0.0387

GnomAD4 exome AF: 0.0371 AC: 6457 AN: 174264 Hom.: 164 Cov.: 0 AF XY: 0.0357 AC XY: 3320 AN XY: 92940

African (AFR) AF: 0.00808 AC: 32 AN: 3962

American (AMR) AF: 0.0338 AC: 222 AN: 6568

Ashkenazi Jewish (ASJ) AF: 0.0316 AC: 146 AN: 4620

East Asian (EAS) AF: 0.000240 AC: 2 AN: 8344

South Asian (SAS) AF: 0.0171 AC: 444 AN: 26010

European-Finnish (FIN) AF: 0.0501 AC: 467 AN: 9328

Middle Eastern (MID) AF: 0.0453 AC: 31 AN: 684

European-Non Finnish (NFE) AF: 0.0448 AC: 4709 AN: 105124

Other (OTH) AF: 0.0420 AC: 404 AN: 9624

GnomAD4 genome AF: 0.0315 AC: 4802 AN: 152354 Hom.: 109 Cov.: 33 AF XY: 0.0318 AC XY: 2368 AN XY: 74506

African (AFR) AF: 0.00851 AC: 354 AN: 41592

American (AMR) AF: 0.0425 AC: 650 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0285 AC: 99 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.0114 AC: 55 AN: 4826

European-Finnish (FIN) AF: 0.0441 AC: 469 AN: 10630

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0444 AC: 3018 AN: 68032

Other (OTH) AF: 0.0383 AC: 81 AN: 2114

Alfa AF: 0.0370 Hom.: 80

Bravo AF: 0.0313

Asia WGS AF: 0.00837 AC: 29 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	8.0
DANN	Benign	0.61
PhyloP100		0.14
PromoterAI		0.083	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs143407873; hg19: chr2-20190159;