chr2-36851080-C-G

Position:

• chr2-36851080-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_003162.4(STRN):​c.2006G>C​(p.Arg669Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,256 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: STRN NM_003162.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.06

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STRN	NM_003162.4	c.2006G>C	p.Arg669Thr	missense_variant	16/18	ENST00000263918.9
STRN	XM_011533073.3	c.2093G>C	p.Arg698Thr	missense_variant	17/19
STRN	XM_005264519.6	c.1895G>C	p.Arg632Thr	missense_variant	15/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STRN	ENST00000263918.9	c.2006G>C	p.Arg669Thr	missense_variant	16/18	1	NM_003162.4	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461256 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726934

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 13, 2024

The c.2006G>C (p.R669T) alteration is located in exon 16 (coding exon 16) of the STRN gene. This alteration results from a G to C substitution at nucleotide position 2006, causing the arginine (R) at amino acid position 669 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Uncertain	0.020	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.23	T;.
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.97	D;D
M_CAP	Benign	0.0098	T
MetaRNN	Uncertain	0.52	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	M;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-3.0	D;D
REVEL	Benign	0.16
Sift	Benign	0.033	D;D
Sift4G	Uncertain	0.031	D;D
Polyphen		0.16	B;P
Vest4		0.72
MutPred		0.55		Loss of catalytic residue at R669 (P = 0.1304);.;
MVP		0.26
MPC		0.15
ClinPred		0.91	D
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.26
gMVP		0.44

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-37078223;