chr2-36851245-G-A

Position:

• chr2-36851245-G-A

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.1979-138C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0179 in 591,568 control chromosomes in the GnomAD database, including 172 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.028 (90 hom., cov: 31)
  • Exomes 𝑓: 0.014 (82 hom.)
• Consequence: STRN NM_003162.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.365

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=-0.9).
• BP6: Variant 2-36851245-G-A is Benign according to our data. Variant chr2-36851245-G-A is described in ClinVar as [Benign]. Clinvar id is 1249012.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0625 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STRN	NM_003162.4	c.1979-138C>T		intron_variant		ENST00000263918.9
STRN	XM_005264519.6	c.1868-138C>T		intron_variant
STRN	XM_011533073.3	c.2066-138C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STRN	ENST00000263918.9	c.1979-138C>T		intron_variant		1	NM_003162.4	P1

Frequencies

GnomAD3 genomes AF: 0.0279 AC: 4243 AN: 152188 Hom.: 89 Cov.: 31

Gnomad AFR AF: 0.0646

Gnomad AMI AF: 0.0603

Gnomad AMR AF: 0.0175

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.0112

Gnomad FIN AF: 0.0222

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0131

Gnomad OTH AF: 0.0196

GnomAD4 exome AF: 0.0144 AC: 6338 AN: 439264 Hom.: 82 AF XY: 0.0138 AC XY: 3227 AN XY: 233846

Gnomad4 AFR exome AF: 0.0705

Gnomad4 AMR exome AF: 0.0114

Gnomad4 ASJ exome AF: 0.00191

Gnomad4 EAS exome AF: 0.000489

Gnomad4 SAS exome AF: 0.0103

Gnomad4 FIN exome AF: 0.0201

Gnomad4 NFE exome AF: 0.0141

Gnomad4 OTH exome AF: 0.0167

GnomAD4 genome AF: 0.0279 AC: 4254 AN: 152304 Hom.: 90 Cov.: 31 AF XY: 0.0270 AC XY: 2013 AN XY: 74466

Gnomad4 AFR AF: 0.0646

Gnomad4 AMR AF: 0.0176

Gnomad4 ASJ AF: 0.00288

Gnomad4 EAS AF: 0.000965

Gnomad4 SAS AF: 0.0116

Gnomad4 FIN AF: 0.0222

Gnomad4 NFE AF: 0.0131

Gnomad4 OTH AF: 0.0194

Alfa AF: 0.0221 Hom.: 9

Bravo AF: 0.0303

Asia WGS AF: 0.00808 AC: 28 AN: 3478

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	clinical testing	GeneDx	May 16, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.4
DANN	Benign	0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs28701005; hg19: chr2-37078388;