2-189661607-C-T

Variant names:

• chr2-189661607-C-T
• rs187165993
• NM_001353493.2:c.87C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001353493.2(ASDURF):​c.87C>T​(p.Ser29Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00795 in 399,366 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0068 (6 hom., cov: 32)
  • Exomes 𝑓: 0.0087 (19 hom.)
• Consequence: ASDURF NM_001353493.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.231
• Publications: 0 publications found

Genes affected

ASDURF (HGNC:53619): (ASNSD1 upstream open reading frame) Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000286165 (HGNC:):

ASNSD1 (HGNC:24910): (asparagine synthetase domain containing 1) Predicted to enable asparagine synthase (glutamine-hydrolyzing) activity. Predicted to be involved in asparagine biosynthetic process and glutamine metabolic process. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 2-189661607-C-T is Benign according to our data. Variant chr2-189661607-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2651759.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.231 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 6 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001353493.2. 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
	ASDURF	NM_001353493.2	MANE Select	c.87C>T	p.Ser29Ser	synonymous	Exon 1 of 4	NP_001340422.1	L0R819-1
	ASNSD1	NM_019048.4	MANE Select	c.-226C>T		5_prime_UTR	Exon 1 of 6	NP_061921.2	Q9NWL6-1
	ASDURF	NM_001353494.2		c.87C>T	p.Ser29Ser	synonymous	Exon 1 of 4	NP_001340423.1	U3KQ49

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASDURF	ENST00000607829.6	TSL:2 MANE Select	c.87C>T	p.Ser29Ser	synonymous	Exon 1 of 4	ENSP00000475224.1	L0R819-1
	ENSG00000286165	ENST00000606910.5	TSL:3	c.87C>T	p.Ser29Ser	synonymous	Exon 1 of 5	ENSP00000476091.1	U3KQP1
	ASNSD1	ENST00000260952.9	TSL:1 MANE Select	c.-226C>T		5_prime_UTR	Exon 1 of 6	ENSP00000260952.4	Q9NWL6-1

Frequencies

GnomAD3 genomes AF: 0.00681 AC: 1037 AN: 152198 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.00150

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00288

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0249

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00956

Gnomad OTH AF: 0.00573

GnomAD2 exomes AF: 0.00850 AC: 73 AN: 8584 AF XY: 0.00985

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad NFE exome AF: 0.00954

Gnomad OTH exome AF: 0.00595

GnomAD4 exome AF: 0.00865 AC: 2137 AN: 247050 Hom.: 19 Cov.: 0 AF XY: 0.00848 AC XY: 1062 AN XY: 125296

African (AFR) AF: 0.00139 AC: 10 AN: 7190

American (AMR) AF: 0.00323 AC: 24 AN: 7436

Ashkenazi Jewish (ASJ) AF: 0.000974 AC: 9 AN: 9242

East Asian (EAS) AF: 0.00 AC: 0 AN: 22908

South Asian (SAS) AF: 0.000329 AC: 1 AN: 3038

European-Finnish (FIN) AF: 0.0248 AC: 528 AN: 21256

Middle Eastern (MID) AF: 0.000772 AC: 1 AN: 1296

European-Non Finnish (NFE) AF: 0.00924 AC: 1462 AN: 158292

Other (OTH) AF: 0.00622 AC: 102 AN: 16392

GnomAD4 genome AF: 0.00681 AC: 1037 AN: 152316 Hom.: 6 Cov.: 32 AF XY: 0.00690 AC XY: 514 AN XY: 74478

African (AFR) AF: 0.00149 AC: 62 AN: 41582

American (AMR) AF: 0.00288 AC: 44 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.0249 AC: 264 AN: 10616

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00956 AC: 650 AN: 68016

Other (OTH) AF: 0.00567 AC: 12 AN: 2116

Alfa AF: 0.00762 Hom.: 2

Bravo AF: 0.00523

Asia WGS AF: 0.00115 AC: 4 AN: 3478

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	-0.55
CADD	Benign	10
DANN	Benign	0.83
PhyloP100		0.23
PromoterAI		-0.018	Neutral
Mutation Taster		=296/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs187165993; hg19: chr2-190526333;