rs910697

Variant names:

• chr1-112520503-A-G
• rs910697
• NM_024494.3:c.1170A>G

Your query was ambiguous. Multiple possible variants found:

• chr1-112520503-A-G
• chr1-112520503-A-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_024494.3(WNT2B):​c.1170A>G​(p.Gln390Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.466 in 1,612,766 control chromosomes in the GnomAD database, including 177,367 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.48 (18157 hom., cov: 31)
  • Exomes 𝑓: 0.46 (159210 hom.)
• Consequence: WNT2B NM_024494.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.46
• Publications: 28 publications found

Genes affected

WNT2B (HGNC:12781): (Wnt family member 2B) This gene encodes a member of the wingless-type MMTV integration site (WNT) family of highly conserved, secreted signaling factors. WNT family members function in a variety of developmental processes including regulation of cell growth and differentiation and are characterized by a WNT-core domain. This gene may play a role in human development as well as carcinogenesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]

ST7L (HGNC:18441): (suppression of tumorigenicity 7 like) This gene was identified by its similarity to the ST7 tumor suppressor gene found in the chromosome 7q31 region. This gene is clustered in a tail-to-tail manner with the WNT2B gene in a chromosomal region known to be deleted and rearranged in a variety of cancers. Several transcript variants encoding many different isoforms have been described, but some have not been fully characterized. [provided by RefSeq, Feb 2011]

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 1-112520503-A-G is Benign according to our data. Variant chr1-112520503-A-G is described in ClinVar as Benign. ClinVar VariationId is 1608306.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.46 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.624 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024494.3. 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
	WNT2B	NM_024494.3	MANE Select	c.1170A>G	p.Gln390Gln	synonymous	Exon 5 of 5	NP_078613.1	Q93097-1
	WNT2B	NM_004185.4		c.1113A>G	p.Gln371Gln	synonymous	Exon 6 of 6	NP_004176.2	Q93097-2
	WNT2B	NM_001291880.1		c.894A>G	p.Gln298Gln	synonymous	Exon 5 of 5	NP_001278809.1	Q93097

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNT2B	ENST00000369684.5	TSL:1 MANE Select	c.1170A>G	p.Gln390Gln	synonymous	Exon 5 of 5	ENSP00000358698.4	Q93097-1
	WNT2B	ENST00000369686.9	TSL:1	c.1113A>G	p.Gln371Gln	synonymous	Exon 6 of 6	ENSP00000358700.4	Q93097-2
	WNT2B	ENST00000870348.1		c.1188A>G	p.Gln396Gln	synonymous	Exon 5 of 5	ENSP00000540407.1

Frequencies

GnomAD3 genomes AF: 0.484 AC: 73529 AN: 151800 Hom.: 18135 Cov.: 31

Gnomad AFR AF: 0.536

Gnomad AMI AF: 0.533

Gnomad AMR AF: 0.444

Gnomad ASJ AF: 0.484

Gnomad EAS AF: 0.642

Gnomad SAS AF: 0.334

Gnomad FIN AF: 0.501

Gnomad MID AF: 0.401

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.446

GnomAD2 exomes AF: 0.473 AC: 117938 AN: 249518 AF XY: 0.463

Gnomad AFR exome AF: 0.529

Gnomad AMR exome AF: 0.486

Gnomad ASJ exome AF: 0.487

Gnomad EAS exome AF: 0.648

Gnomad FIN exome AF: 0.498

Gnomad NFE exome AF: 0.462

Gnomad OTH exome AF: 0.464

GnomAD4 exome AF: 0.464 AC: 678397 AN: 1460848 Hom.: 159210 Cov.: 47 AF XY: 0.459 AC XY: 333912 AN XY: 726698

African (AFR) AF: 0.532 AC: 17804 AN: 33440

American (AMR) AF: 0.487 AC: 21690 AN: 44580

Ashkenazi Jewish (ASJ) AF: 0.482 AC: 12585 AN: 26126

East Asian (EAS) AF: 0.638 AC: 25319 AN: 39662

South Asian (SAS) AF: 0.342 AC: 29472 AN: 86198

European-Finnish (FIN) AF: 0.501 AC: 26731 AN: 53354

Middle Eastern (MID) AF: 0.460 AC: 2651 AN: 5768

European-Non Finnish (NFE) AF: 0.463 AC: 514106 AN: 1111368

Other (OTH) AF: 0.465 AC: 28039 AN: 60352

GnomAD4 genome AF: 0.484 AC: 73582 AN: 151918 Hom.: 18157 Cov.: 31 AF XY: 0.485 AC XY: 35972 AN XY: 74238

African (AFR) AF: 0.536 AC: 22179 AN: 41402

American (AMR) AF: 0.444 AC: 6792 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.484 AC: 1677 AN: 3466

East Asian (EAS) AF: 0.642 AC: 3298 AN: 5136

South Asian (SAS) AF: 0.333 AC: 1602 AN: 4810

European-Finnish (FIN) AF: 0.501 AC: 5296 AN: 10564

Middle Eastern (MID) AF: 0.411 AC: 120 AN: 292

European-Non Finnish (NFE) AF: 0.459 AC: 31202 AN: 67944

Other (OTH) AF: 0.443 AC: 932 AN: 2104

Alfa AF: 0.474 Hom.: 14015

Bravo AF: 0.485

Asia WGS AF: 0.467 AC: 1624 AN: 3478

ClinVar

ClinVar submissions

Significance: 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	-0.61
CADD	Benign	7.5
DANN	Benign	0.73
PhyloP100		1.5
Mutation Taster		=99/1	polymorphism (auto)

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: rs910697; hg19: chr1-113063125; COSMIC: COSV56677579; COSMIC: COSV56677579;