2-216464684-T-C

Variant names:

• chr2-216464684-T-C
• rs2066516
• NM_014140.4:c.2141+17T>C

Variant summary

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

The NM_014140.4(SMARCAL1):​c.2141+17T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00507 in 1,559,052 control chromosomes in the GnomAD database, including 232 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.023 (135 hom., cov: 32)
  • Exomes 𝑓: 0.0031 (97 hom.)
• Consequence: SMARCAL1 NM_014140.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.578
• Publications: 1 publications found

Genes affected

SMARCAL1 (HGNC:11102): (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a like 1) The protein encoded by this gene is a member of the SWI/SNF family of proteins. Members of this family have helicase and ATPase activities and are thought to regulate transcription of certain genes by altering the chromatin structure around those genes. The encoded protein shows sequence similarity to the E. coli RNA polymerase-binding protein HepA. Mutations in this gene are a cause of Schimke immunoosseous dysplasia (SIOD), an autosomal recessive disorder with the diagnostic features of spondyloepiphyseal dysplasia, renal dysfunction, and T-cell immunodeficiency. [provided by RefSeq, Jul 2008]

SMARCAL1 Gene-Disease associations (from GenCC):

• Schimke immuno-osseous dysplasia

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 2-216464684-T-C is Benign according to our data. Variant chr2-216464684-T-C is described in ClinVar as Benign. ClinVar VariationId is 260342.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0759 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMARCAL1	NM_014140.4	c.2141+17T>C		intron_variant	Intron 13 of 17	ENST00000357276.9	NP_054859.2
SMARCAL1	NM_001127207.2	c.2141+17T>C		intron_variant	Intron 13 of 17		NP_001120679.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMARCAL1	ENST00000357276.9	c.2141+17T>C		intron_variant	Intron 13 of 17	2	NM_014140.4	ENSP00000349823.4

Frequencies

GnomAD3 genomes AF: 0.0230 AC: 3481 AN: 151390 Hom.: 135 Cov.: 32

Gnomad AFR AF: 0.0783

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0109

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000285

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000971

Gnomad OTH AF: 0.0168

GnomAD2 exomes AF: 0.00645 AC: 1610 AN: 249482 AF XY: 0.00495

Gnomad AFR exome AF: 0.0811

Gnomad AMR exome AF: 0.00422

Gnomad ASJ exome AF: 0.0000994

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000250

Gnomad NFE exome AF: 0.000986

Gnomad OTH exome AF: 0.00360

GnomAD4 exome AF: 0.00313 AC: 4412 AN: 1407544 Hom.: 97 Cov.: 25 AF XY: 0.00275 AC XY: 1936 AN XY: 703544

African (AFR) AF: 0.0802 AC: 2585 AN: 32212

American (AMR) AF: 0.00464 AC: 207 AN: 44646

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25814

East Asian (EAS) AF: 0.00 AC: 0 AN: 39416

South Asian (SAS) AF: 0.000176 AC: 15 AN: 85154

European-Finnish (FIN) AF: 0.000155 AC: 8 AN: 51606

Middle Eastern (MID) AF: 0.00177 AC: 10 AN: 5654

European-Non Finnish (NFE) AF: 0.00120 AC: 1278 AN: 1064520

Other (OTH) AF: 0.00528 AC: 309 AN: 58522

GnomAD4 genome AF: 0.0230 AC: 3486 AN: 151508 Hom.: 135 Cov.: 32 AF XY: 0.0218 AC XY: 1615 AN XY: 74014

African (AFR) AF: 0.0782 AC: 3215 AN: 41124

American (AMR) AF: 0.0109 AC: 166 AN: 15210

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5146

South Asian (SAS) AF: 0.00 AC: 0 AN: 4792

European-Finnish (FIN) AF: 0.000285 AC: 3 AN: 10514

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.000971 AC: 66 AN: 67942

Other (OTH) AF: 0.0166 AC: 35 AN: 2108

Alfa AF: 0.00546 Hom.: 21

Bravo AF: 0.0259

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Mar 02, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Schimke immuno-osseous dysplasia Benign:2

Jan 31, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Nov 29, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not specified Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.084
DANN	Benign	0.42
PhyloP100		-0.58
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2066516; hg19: chr2-217329407;