7-117297673-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_003391.3(WNT2):c.792G>A(p.Thr264=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00232 in 1,614,092 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0055 (5 hom., cov: 32)
  • Exomes 𝑓: 0.0020 (11 hom.)
• Consequence: WNT2 NM_003391.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.178

Genes affected

WNT2 (HGNC:12780): (Wnt family member 2) This gene is a member of the WNT gene family. The WNT gene family consists of structurally related genes which encode secreted signaling proteins. These proteins have been implicated in oncogenesis and in several developmental processes, including regulation of cell fate and patterning during embryogenesis. Alternatively spliced transcript variants have been identified for this gene. [provided by RefSeq, Jul 2008]

LOC124900596 (HGNC:):

CFTR (HGNC:1884): (CF transmembrane conductance regulator) This gene encodes a member of the ATP-binding cassette (ABC) transporter superfamily. The encoded protein functions as a chloride channel, making it unique among members of this protein family, and controls ion and water secretion and absorption in epithelial tissues. Channel activation is mediated by cycles of regulatory domain phosphorylation, ATP-binding by the nucleotide-binding domains, and ATP hydrolysis. Mutations in this gene cause cystic fibrosis, the most common lethal genetic disorder in populations of Northern European descent. The most frequently occurring mutation in cystic fibrosis, DeltaF508, results in impaired folding and trafficking of the encoded protein. Multiple pseudogenes have been identified in the human genome. [provided by RefSeq, Aug 2017]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 7-117297673-C-T is Benign according to our data. Variant chr7-117297673-C-T is described in ClinVar as [Benign]. Clinvar id is 774454.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.178 with no splicing effect.
• BS2: High AC in GnomAd at 838 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WNT2	NM_003391.3	c.792G>A	p.Thr264=	synonymous_variant	4/5	ENST00000265441.8
LOC124900596	XR_927899.3	n.40-717C>T		intron_variant, non_coding_transcript_variant
WNT2	NR_024047.2	n.797G>A		non_coding_transcript_exon_variant	4/5
LOC124900596	XR_927898.3	n.83-717C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WNT2	ENST00000265441.8	c.792G>A	p.Thr264=	synonymous_variant	4/5	1	NM_003391.3	P1

Frequencies

GnomAD3 genomes AF: 0.00551 AC: 838 AN: 152152 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.0144

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00622

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00190

Gnomad OTH AF: 0.00862

GnomAD3 exomes AF: 0.00230 AC: 577 AN: 251410 Hom.: 4 AF XY: 0.00191 AC XY: 259 AN XY: 135872

Gnomad AFR exome AF: 0.0145

Gnomad AMR exome AF: 0.00309

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00179

Gnomad OTH exome AF: 0.00408

GnomAD4 exome AF: 0.00199 AC: 2906 AN: 1461822 Hom.: 11 Cov.: 31 AF XY: 0.00195 AC XY: 1415 AN XY: 727200

Gnomad4 AFR exome AF: 0.0145

Gnomad4 AMR exome AF: 0.00344

Gnomad4 ASJ exome AF: 0.0000765

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000197

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00183

Gnomad4 OTH exome AF: 0.00316

GnomAD4 genome AF: 0.00550 AC: 838 AN: 152270 Hom.: 5 Cov.: 32 AF XY: 0.00509 AC XY: 379 AN XY: 74438

Gnomad4 AFR AF: 0.0143

Gnomad4 AMR AF: 0.00621

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00190

Gnomad4 OTH AF: 0.00853

Alfa AF: 0.00325 Hom.: 2

Bravo AF: 0.00668

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.00185

EpiControl AF: 0.00160

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 13, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
Cadd	Benign	5.8
Dann	Benign	0.79

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

Publications

LitVar

Other links and lift over

dbSNP: rs61736336; hg19: chr7-116937727; COSMIC: COSV104545881; COSMIC: COSV104545881;