2-36849451-T-C

Position:

• chr2-36849451-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003162.4(STRN):​c.*5A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 1,613,422 control chromosomes in the GnomAD database, including 16,337 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1695 hom., cov: 32)
  • Exomes 𝑓: 0.11 (14642 hom.)
• Consequence: STRN NM_003162.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.09

Genes affected

STRN (HGNC:11424): (striatin) Enables armadillo repeat domain binding activity; estrogen receptor binding activity; and protein phosphatase 2A binding activity. Involved in Wnt signaling pathway and negative regulation of cell population proliferation. Located in bicellular tight junction. Part of FAR/SIN/STRIPAK complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 2-36849451-T-C is Benign according to our data. Variant chr2-36849451-T-C is described in ClinVar as [Benign]. Clinvar id is 1275078.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.536 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STRN	NM_003162.4	c.*5A>G		3_prime_UTR_variant	18/18	ENST00000263918.9
STRN	XM_005264519.6	c.*5A>G		3_prime_UTR_variant	17/17
STRN	XM_011533073.3	c.*5A>G		3_prime_UTR_variant	19/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STRN	ENST00000263918.9	c.*5A>G		3_prime_UTR_variant	18/18	1	NM_003162.4	P1

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18064 AN: 152050 Hom.: 1685 Cov.: 32

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.552

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0894

Gnomad OTH AF: 0.114

GnomAD3 exomes AF: 0.152 AC: 38223 AN: 250648 Hom.: 4650 AF XY: 0.149 AC XY: 20162 AN XY: 135464

Gnomad AFR exome AF: 0.104

Gnomad AMR exome AF: 0.195

Gnomad ASJ exome AF: 0.114

Gnomad EAS exome AF: 0.533

Gnomad SAS exome AF: 0.169

Gnomad FIN exome AF: 0.117

Gnomad NFE exome AF: 0.0912

Gnomad OTH exome AF: 0.139

GnomAD4 exome AF: 0.113 AC: 164771 AN: 1461254 Hom.: 14642 Cov.: 32 AF XY: 0.114 AC XY: 82807 AN XY: 726932

Gnomad4 AFR exome AF: 0.106

Gnomad4 AMR exome AF: 0.191

Gnomad4 ASJ exome AF: 0.110

Gnomad4 EAS exome AF: 0.579

Gnomad4 SAS exome AF: 0.170

Gnomad4 FIN exome AF: 0.118

Gnomad4 NFE exome AF: 0.0880

Gnomad4 OTH exome AF: 0.125

GnomAD4 genome AF: 0.119 AC: 18090 AN: 152168 Hom.: 1695 Cov.: 32 AF XY: 0.124 AC XY: 9237 AN XY: 74396

Gnomad4 AFR AF: 0.102

Gnomad4 AMR AF: 0.139

Gnomad4 ASJ AF: 0.110

Gnomad4 EAS AF: 0.552

Gnomad4 SAS AF: 0.182

Gnomad4 FIN AF: 0.111

Gnomad4 NFE AF: 0.0894

Gnomad4 OTH AF: 0.119

Alfa AF: 0.0982 Hom.: 440

Bravo AF: 0.123

Asia WGS AF: 0.329 AC: 1142 AN: 3478

EpiCase AF: 0.0895

EpiControl AF: 0.0903

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 05, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.6
DANN	Benign	0.56

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: rs62132521; hg19: chr2-37076594; COSMIC: COSV55746721;