rs2244182

Variant names:

• chr2-105361446-G-C
• rs2244182
• NM_001318895.3:c.689-12C>G

Your query was ambiguous. Multiple possible variants found:

• chr2-105361446-G-C
• chr2-105361446-G-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001318895.3(FHL2):​c.689-12C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 1,606,806 control chromosomes in the GnomAD database, including 27,056 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (4349 hom., cov: 33)
  • Exomes 𝑓: 0.16 (22707 hom.)
• Consequence: FHL2 NM_001318895.3 intron
• Scores: Splicing: ADA: 0.0005900
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.861
• Publications: 6 publications found

Genes affected

FHL2 (HGNC:3703): (four and a half LIM domains 2) This gene encodes a member of the four-and-a-half-LIM-only protein family. Family members contain two highly conserved, tandemly arranged, zinc finger domains with four highly conserved cysteines binding a zinc atom in each zinc finger. This protein is thought to have a role in the assembly of extracellular membranes. Also, this gene is down-regulated during transformation of normal myoblasts to rhabdomyosarcoma cells and the encoded protein may function as a link between presenilin-2 and an intracellular signaling pathway. Multiple alternatively spliced variants encoding different isoforms have been identified. [provided by RefSeq, Jan 2016]

C2orf49 (HGNC:28772): (chromosome 2 open reading frame 49) Predicted to be involved in embryonic morphogenesis. Located in nucleus. Part of tRNA-splicing ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 2-105361446-G-C is Benign according to our data. Variant chr2-105361446-G-C is described in ClinVar as Benign. ClinVar VariationId is 48329.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.525 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001318895.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FHL2	NM_001318895.3	MANE Select	c.689-12C>G		intron	N/A	NP_001305824.1	Q14192-1
	FHL2	NM_001039492.3		c.689-12C>G		intron	N/A	NP_001034581.1	Q6I9R8
	FHL2	NM_001318894.1		c.689-12C>G		intron	N/A	NP_001305823.1	Q2XQU9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FHL2	ENST00000530340.6	TSL:1 MANE Select	c.689-12C>G		intron	N/A	ENSP00000433567.2	Q14192-1
	FHL2	ENST00000322142.13	TSL:1	c.689-12C>G		intron	N/A	ENSP00000322909.8	Q14192-1
	FHL2	ENST00000344213.9	TSL:1	c.689-12C>G		intron	N/A	ENSP00000344266.5	Q14192-1

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32315 AN: 152008 Hom.: 4347 Cov.: 33

Gnomad AFR AF: 0.333

Gnomad AMI AF: 0.0746

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.542

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.205

GnomAD2 exomes AF: 0.210 AC: 51251 AN: 244478 AF XY: 0.199

Gnomad AFR exome AF: 0.347

Gnomad AMR exome AF: 0.284

Gnomad ASJ exome AF: 0.133

Gnomad EAS exome AF: 0.564

Gnomad FIN exome AF: 0.137

Gnomad NFE exome AF: 0.133

Gnomad OTH exome AF: 0.185

GnomAD4 exome AF: 0.157 AC: 228479 AN: 1454680 Hom.: 22707 Cov.: 31 AF XY: 0.156 AC XY: 113016 AN XY: 723240

African (AFR) AF: 0.336 AC: 11159 AN: 33200

American (AMR) AF: 0.273 AC: 11974 AN: 43828

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 3534 AN: 25910

East Asian (EAS) AF: 0.526 AC: 20802 AN: 39544

South Asian (SAS) AF: 0.196 AC: 16737 AN: 85270

European-Finnish (FIN) AF: 0.140 AC: 7484 AN: 53330

Middle Eastern (MID) AF: 0.135 AC: 771 AN: 5720

European-Non Finnish (NFE) AF: 0.131 AC: 145054 AN: 1107752

Other (OTH) AF: 0.182 AC: 10964 AN: 60126

GnomAD4 genome AF: 0.213 AC: 32349 AN: 152126 Hom.: 4349 Cov.: 33 AF XY: 0.215 AC XY: 15996 AN XY: 74378

African (AFR) AF: 0.333 AC: 13815 AN: 41492

American (AMR) AF: 0.216 AC: 3295 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.129 AC: 449 AN: 3472

East Asian (EAS) AF: 0.541 AC: 2799 AN: 5170

South Asian (SAS) AF: 0.199 AC: 959 AN: 4826

European-Finnish (FIN) AF: 0.136 AC: 1436 AN: 10568

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.133 AC: 9036 AN: 68012

Other (OTH) AF: 0.211 AC: 446 AN: 2112

Alfa AF: 0.171 Hom.: 502

Bravo AF: 0.229

Asia WGS AF: 0.363 AC: 1263 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)
-	-	1	Primary dilated cardiomyopathy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	12
DANN	Benign	0.66
PhyloP100		0.86
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00059
dbscSNV1_RF	Benign	0.062
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2244182;

hg19: chr2-105977903;

COSMIC: COSV59078969;

COSMIC: COSV59078969;