2-105396175-C-T

Position:

• chr2-105396175-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001318895.3(FHL2):​c.-25+472G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.705 in 152,132 control chromosomes in the GnomAD database, including 37,989 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.71 (37989 hom., cov: 32)
• Consequence: FHL2 NM_001318895.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.392

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.751 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FHL2	NM_001318895.3	c.-25+472G>A		intron_variant		ENST00000530340.6	NP_001305824.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FHL2	ENST00000530340.6	c.-25+472G>A		intron_variant		1	NM_001318895.3	ENSP00000433567	P1

Frequencies

GnomAD3 genomes AF: 0.705 AC: 107216 AN: 152014 Hom.: 37969 Cov.: 32

Gnomad AFR AF: 0.758

Gnomad AMI AF: 0.719

Gnomad AMR AF: 0.748

Gnomad ASJ AF: 0.745

Gnomad EAS AF: 0.678

Gnomad SAS AF: 0.633

Gnomad FIN AF: 0.756

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.660

Gnomad OTH AF: 0.712

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.705 AC: 107288 AN: 152132 Hom.: 37989 Cov.: 32 AF XY: 0.710 AC XY: 52790 AN XY: 74372

Gnomad4 AFR AF: 0.758

Gnomad4 AMR AF: 0.748

Gnomad4 ASJ AF: 0.745

Gnomad4 EAS AF: 0.678

Gnomad4 SAS AF: 0.634

Gnomad4 FIN AF: 0.756

Gnomad4 NFE AF: 0.660

Gnomad4 OTH AF: 0.710

Alfa AF: 0.666 Hom.: 32536

Bravo AF: 0.711

Asia WGS AF: 0.648 AC: 2256 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.98
DANN	Benign	0.53

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: rs4851765; hg19: chr2-106012632; COSMIC: COSV59079215;