1-112521149-C-T

Variant names:

• chr1-112521149-C-T
• rs2273368
• NM_024494.3:c.*640C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024494.3(WNT2B):​c.*640C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 152,868 control chromosomes in the GnomAD database, including 3,326 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.19 (3304 hom., cov: 31)
  • Exomes 𝑓: 0.20 (22 hom.)
• Consequence: WNT2B NM_024494.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.497
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.443 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNT2B	NM_024494.3	MANE Select	c.*640C>T		3_prime_UTR	Exon 5 of 5	NP_078613.1
	WNT2B	NM_004185.4		c.*640C>T		3_prime_UTR	Exon 6 of 6	NP_004176.2
	WNT2B	NM_001291880.1		c.*640C>T		3_prime_UTR	Exon 5 of 5	NP_001278809.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNT2B	ENST00000369684.5	TSL:1 MANE Select	c.*640C>T		3_prime_UTR	Exon 5 of 5	ENSP00000358698.4
	WNT2B	ENST00000369686.9	TSL:1	c.*640C>T		3_prime_UTR	Exon 6 of 6	ENSP00000358700.4
	WNT2B	ENST00000870348.1		c.*640C>T		3_prime_UTR	Exon 5 of 5	ENSP00000540407.1

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28293 AN: 151854 Hom.: 3302 Cov.: 31

Gnomad AFR AF: 0.0762

Gnomad AMI AF: 0.294

Gnomad AMR AF: 0.253

Gnomad ASJ AF: 0.258

Gnomad EAS AF: 0.458

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.194

Gnomad OTH AF: 0.184

GnomAD4 exome AF: 0.201 AC: 180 AN: 896 Hom.: 22 Cov.: 0 AF XY: 0.210 AC XY: 94 AN XY: 448

African (AFR) AF: 0.00 AC: 0 AN: 4

American (AMR) AF: 0.309 AC: 50 AN: 162

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.306 AC: 11 AN: 36

European-Finnish (FIN) AF: 0.167 AC: 1 AN: 6

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.173 AC: 115 AN: 666

Other (OTH) AF: 0.136 AC: 3 AN: 22

GnomAD4 genome AF: 0.186 AC: 28297 AN: 151972 Hom.: 3304 Cov.: 31 AF XY: 0.195 AC XY: 14473 AN XY: 74280

African (AFR) AF: 0.0761 AC: 3157 AN: 41486

American (AMR) AF: 0.254 AC: 3871 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.258 AC: 892 AN: 3464

East Asian (EAS) AF: 0.458 AC: 2359 AN: 5148

South Asian (SAS) AF: 0.209 AC: 1006 AN: 4822

European-Finnish (FIN) AF: 0.296 AC: 3116 AN: 10532

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.194 AC: 13206 AN: 67954

Other (OTH) AF: 0.182 AC: 385 AN: 2112

Alfa AF: 0.184 Hom.: 5071

Bravo AF: 0.184

Asia WGS AF: 0.312 AC: 1081 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.39
DANN	Benign	0.36
PhyloP100		-0.50
Mutation Taster		=100/0	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: rs2273368; hg19: chr1-113063771;