2-19990398-C-A

Position:

• chr2-19990398-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NR_110235.1(WDR35-DT):​n.195C>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 NR_110235.1 non_coding_transcript_exon
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.141

Genes affected

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

ACMG classification

Verdict is Benign. Variant got -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 id 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 male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 109 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR35-DT	NR_110235.1	n.195C>A		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR35-DT	ENST00000416575.2	n.188C>A		non_coding_transcript_exon_variant	1/3	2
WDR35-DT	ENST00000658200.1	n.190C>A		non_coding_transcript_exon_variant	1/3

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

Gnomad4 AFR exome AF: 0.00808

Gnomad4 AMR exome AF: 0.0338

Gnomad4 ASJ exome AF: 0.0316

Gnomad4 EAS exome AF: 0.000240

Gnomad4 SAS exome AF: 0.0171

Gnomad4 FIN exome AF: 0.0501

Gnomad4 NFE exome AF: 0.0448

Gnomad4 OTH exome AF: 0.0420

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

Gnomad4 AFR AF: 0.00851

Gnomad4 AMR AF: 0.0425

Gnomad4 ASJ AF: 0.0285

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0114

Gnomad4 FIN AF: 0.0441

Gnomad4 NFE AF: 0.0444

Gnomad4 OTH AF: 0.0383

Alfa AF: 0.0383 Hom.: 31

Bravo AF: 0.0313

Asia WGS AF: 0.00837 AC: 29 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 09, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	8.0
DANN	Benign	0.61

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs143407873; hg19: chr2-20190159;